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House dust mites (HDM) are common aeroallergens linked to airway inflammation and remodeling in asthma. Protease-activated receptor 2 (PAR2) and thymic stromal lymphopoietin (TSLP) may mediate these immune responses. However, how the epithelium influences fibroblasts toward airway remodeling remains unclear. We hypothesize that HDM stimulates human bronchial epithelial cells (HBECs) to produce TSLP via PAR2 activation, driving fibroblasts toward remodeling processes. HBECs were treated with HDM, with or without the PAR2 antagonist FSLLRY-NH2 (FSL), and TSLP expression was measured by qPCR and ELISA. Phosphorylation of MAPKs was assessed by western blotting. Human lung fibroblasts (HLFs) were exposed to recombinant TSLP or conditioned medium (CM) from HDM-stimulated HBECs, with or without anti-TSLP antibodies. Fibroblast proliferation and collagen production were assessed as remodeling markers. HDM increased ERK phosphorylation (not p38 or JNK) and TSLP expression at mRNA and protein levels. FSL preincubation significantly reduced ERK phosphorylation and TSLP production: HDM-stimulated CM induced fibroblast proliferation and collagen production, effects suppressed by anti-TSLP or FSL. Direct treatment with recombinant TSLP also promoted fibroblast proliferation and collagen synthesis. These findings suggest that HDM promotes HBEC-to-HLF paracrine interactions via PAR2-ERK-TSLP axis, participating in airway remodeling. PAR2 antagonists may represent potential therapeutic targets for HDM-induced remodeling processes., Competing Interests: Declarations Conflict of interest All authors declare that they have no conflict of interest. Ethics approval This study was approved by the Institutional Review Board of Taipei Veterans General Hospital (ID 2019-08-004B)., (© 2024. The Author(s).)

Asthma is a complex inflammatory airway disease that arises from the interplay between genetic predisposition and environmental influences. Leucine-rich repeat kinase 2 (LRRK2), a gene commonly associated with Parkinson's disease, has recently gained attention for its role in immune regulation and inflammation beyond the brain. However, its involvement in asthma has not yet been reported. In this study, we used LRRK2 G2019S transgenic mice and LRRK2 knockout mice to establish asthmatic models to explore LRRK2 impact on asthma. We found that LRRK2 G2019S transgenic mice showed exacerbated airway hyperresponsiveness (AHR) and airway inflammation in asthma mouse models induced by house dust mite. RNA sequencing data unveiled that the LRRK2 G2019S mutation enhanced immune response pathways, including NOD-like receptor, cellular response to interferon β and activation of innate immune response signaling. Conversely, LRRK2 deficiency attenuated AHR and airway inflammation in the same asthma models. Our study offers new insights into the role of LRRK2 in allergic inflammation and highlights its potential as a therapeutic target for asthma., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: Hyssopus cuspidatus Boriss., a classic Uyghur medicine, is used to treat inflammatory lung diseases such as asthma. But the therapeutic effect and mechanism of the volatile oil of Hyssopus cuspidatus Boriss.(HVO) in asthma therapy remain unclear., Aim of the Study: We aim to characterize the constituents of HVO, investigate the therapeutic effect in OVA-induced allergic asthmatic mice and further explore the molecular mechanism., Materials and Methods: In this study, we applied two-dimensional gas chromatography quadrupole time-of-flight mass spectrometry (GC × GC-QTOF MS) to identify the ingredients of HVO. We established OVA-induced asthmatic model to investigate the therapeutic effect of HVO. To further explore the potential molecular pathways, we used network pharmacology approach to perform GO and KEGG pathways enrichment, and then built an ingredient-target-pathway network to identify key molecular pathways. Finally, LPS-induced RAW 264.7 macrophages and OVA-induced asthmatic model were used to validate the potential signaling pathways., Results: GC × GC-QTOF MS analysis revealed the presence of 123 compounds of HVO. The sesquiterpenes and monoterpenes are the main constituents. The in vivo study indicated that HVO suppressed OVA-induced eosinophilic infiltration in lung tissues, inhibited the elevation of IgE, IL-4, IL-5, and IL-13 levels, downregulated the expressions of phosphorylated PI3K, Akt, JNK and P38, and maintained epithelial barrier integrity via reducing the degradation of occludin, Zo-1, Zo-2, and E-cadherin. The in vitro study also revealed an inhibition of NO release and downregulation of phosphorylated PI3K, Akt, JNK and P38 levels., Conclusion: HVO alleviates airway inflammation in OVA-induced asthmatic mice by inhibiting PI3K/Akt/JNK/P38 signaling pathway and maintaining airway barrier integrity via reducing the degradation of occludin, Zo-1, Zo-2, and E-cadherin., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Establishing the interaction between aeroallergens and air pollution in children with house dust mite induced allergic rhinitis (HDM-AR) remains challenging, especially in urban areas. The coronavirus disease 2019 (COVID-19) pandemic and the subsequent lockdown measures provided a valuable opportunity., Methods: We analyzed the clinical data of HDM-AR children between March and August in 2018-2020, and classified the children according to the type and the degree of HDM sensitization. The records of patients' hospital visits, allergic rhinitis symptoms assessments, and air pollution measurements in Shanghai were used to assess the differences before (2018-2019) and during the pandemic (2020), as well as during lockdown (March-June) and unlockdown (July-August) period in 2020., Results: The study included 1570 HDM-AR children aged 2 to 8 years old, 815 (51.9%) were monosensitized to HDM (mono-HDM-AR), and 755 (48.1%) were polysensitized to HDM (poly-HDM-AR). There was a significant increase in the rate of clinical visits among children with HDM-AR during the COVID-19 pandemic compared to pre-pandemic (P < 0.001), particularly among older children aged 7-8 years (P = 0.01). During the unlockdown period, there was a notable decrease in clinical visits for children with poly-HDM-AR (P < 0.001). Children with high levels of HDM sensitization exhibited significant symptom improvement in unlockdown period (P < 0.001). Although the air pollutants concentration had improved during the study, there was no effect on the improvement of HDM-AR children as expected., Conclusions: The COVID-19 pandemic and its associated lockdown measures provided a unique context to observe the dynamics of management in children with HDM-AR. The findings underscore the complexity of managing allergic conditions in pediatric populations, highlighting the influence of environmental and lifestyle changes on disease presentation and the need for tailored approaches to treatment during periods of societal disruption., (© 2024. The Author(s).)

The mechanisms that guide T helper 2 (T H 2) cell differentiation in barrier tissues are unclear. Here we describe the molecular pathways driving allergen-specific T H 2 cells using temporal, spatial and single-cell transcriptomic tracking of house dust mite-specific T cells in mice. Differentiation and migration of lung allergen-specific T H 2 cells requires early expression of the transcriptional repressor Blimp-1. Loss of Blimp-1 during priming in the lymph node ablated the formation of T H 2 cells in the lung, indicating early Blimp-1 promotes T H 2 cells with migratory capability. IL-2/STAT5 signals and autocrine/paracrine IL-10 from house dust mite-specific T cells were essential for Blimp-1 and subsequent GATA3 upregulation through repression of Bcl6 and Bach2. Spatial microniches of IL-2 in the lymph node supported the earliest Blimp-1 + T H 2 cells, demonstrating lymph node localization is a driver of T H 2 initiation. Our findings identify an early requirement for IL-2-mediated spatial microniches that integrate with allergen-driven IL-10 from responding T cells to drive allergic asthma., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

The house dust mite is the principal source of aero-allergen worldwide. Exposure to mite-derived allergens is associated with the development of asthma in susceptible individuals, and the majority of asthmatics are allergic to the mite. Mite-derived allergens are functionally diverse and activate multiple cell types within the lung that result in chronic inflammation. Allergens activate store-operated Ca 2+ release-activated Ca 2+ (CRAC) channels, which are widely expressed in multiple cell types within the lung that are associated with the pathogenesis of asthma. Opening of CRAC channels stimulates Ca 2+ -dependent transcription factors, including nuclear factor of activated T cells and nuclear factor-κB, which drive expression of a plethora of pro-inflammatory cytokines and chemokines that help to sustain chronic inflammation. Here, I describe drivers of asthma, properties of mite-derived allergens, how the allergens are recognized by cells, the signalling pathways used by the receptors and how these are transduced into functional effects, with a focus on CRAC channels. In vivo experiments that demonstrate the effectiveness of targeting CRAC channels as a potential new therapy for treating mite-induced asthma are also discussed, in tandem with other possible approaches., (© 2023 The Authors. The Journal of Physiology © 2023 The Physiological Society.)

Objective: To evaluate the benefits of combining omalizumab with specific immunotherapy (SCIT) in the treatment of children with bronchial asthma., Methods: In this study, 83 children with asthma were treated at the Allergy Department of Qingdao University from January 2019 to February 2020. Participants were divided into three groups: SCIT, combination (omalizumab + SCIT), and control (standard asthma medications). We assessed Asthma Control Questionnaire (ACQ) scores, Visual Analogue Scale (VAS) scores, and lung function at baseline, 24 wk, and 48 wk. Additionally, asthma medication scores were compared at 24 and 48 wk. Adverse reactions were monitored in both the SCIT and combination groups., Results: The combination group demonstrated lower ACQ scores at both 24 and 48 wk, and improved VAS scores at 48 wk compared to the other groups. Additionally, lung function parameters (FEV1 and FEF50) showed significant improvement in the combination group. Reduced asthma medication scores were noted in the combination group at 24 and 48 wk. Local adverse reactions were fewer in the combination group, and no systemic adverse reactions were reported., Conclusion: Combining omalizumab with SCIT provides quicker asthma control, lowers medication requirements, and enhances lung function with fewer adverse effects, making it a safe and effective treatment for children with bronchial asthma.

Objective: We analyzed the impact of different inhalant allergens on T-lymphocyte subsets in patients diagnosed with bronchial asthma., Methods: The study included 57 bronchial asthma patients and 22 healthy controls. Asthma patients were categorized into dust mite, animal hair, pollen, and mold groups. Flow cytometry was used to measure the cells in the case group and control group. These T-lymphocyte subset markers were evaluated among patients with bronchial asthma caused by different allergens as well as between the case group and control group., Results: Peripheral blood CD4 + T-cells, CD8 + T-cells, CD4/CD8 ratio, and Th17/Treg ratios were all higher in the case group than in the control group ( p  < 0.05). Peripheral blood T-lymphocyte subsets were compared among the four groups, and it was found that there were statistical differences in the Th17/Treg ratio among the four groups ( p  < 0.05). There were no significant differences observed among the four groups in terms of CD3+ cells, CD4+ cells, CD8+ cells, Th1 cells, Th2 cells, Th17 cells, Treg cells, Th9 cells, and Th22 cells. Further pairwise comparison was made, and the results suggested that the peripheral blood Th17/Treg ratio in the pollen mixed group was lower than that in the dust mite mixed group, animal hair mixed group, and mold mixed group ( p  < 0.05)., Conclusion: Patients with bronchial asthma show varied T-lymphocyte subset responses to different inhalant allergens. Elevated CD4+ T cells and Th17 cells in peripheral blood could indicate asthma risk. However, small sample size may introduce bias to these findings.

Background: Knowledge of the effectiveness of house dust mite (HDM) sublingual immunotherapy (SLIT) in allergic rhinitis (AR) and asthma associated sleep disorders remains incomplete. A noninterventional study was conducted to assess the effect of the standardized quality (SQ) HDM SLIT tablet on safety and symptoms in adults with respiratory allergies caused by HDM. The study also assessed the status of insomnia and daytime sleepiness in patients with AR and/or asthma-associated sleep disorders treated with the SQ HDM SLIT tablet., Methods: This was a 12-month multicenter, longitudinal, and prospective study. Participants started the SQ HDM SLIT tablet for moderateto-severe HDM-induced AR that was persistent despite the use of symptom relieving medication or HDM-induced asthma-associated sleep disorders that were not well controlled with inhaled corticosteroids and were associated with mild-to-severe HDM-induced AR. Sleep symptoms were measured using the Insomnia Severity Index (ISI) questionnaire and the Epworth Sleepiness Scale (ESS)., Results: A total of 1526 adult patients were enrolled, and 1483 were eventually included in the analysis. At baseline, 41.5% of patients reported sleep disorders; of these, 77.0% had insomnia and 28.9% experienced excessive daytime sleepiness. Insomnia was significantly more frequent among patients with uncontrolled AR (83.1%) than among those with controlled AR (52.6%) (P<.0001). Over time, 48.3% and 59.7% of patients, respectively, reported an improvement greater than the minimal clinically important difference in the ISI and ESS scales., Conclusion: In patients with HDM-induced AR and/or asthma-associated sleep disorders, an improvement in subjective insomnia and sleepiness was observed after 1 year of treatment with the SQ HDM SLIT tablet in a real-life setting.

Asthma susceptibility is linked to dysbiosis in early-life gut microbiota, and the antibody secretory immunoglobulin (Ig)A (SIgA) is a key determinant of gut microbiota composition. SIgA is obtained through breast milk during the critical early-life window. We use a mouse model of SIgA deficiency and the house dust mite (HDM) model of asthma to elucidate the role of maternal SIgA in modulating the early-life gut microbiota and asthma protection. Mice that do not receive maternal SIgA display a transient bloom of segmented filamentous bacteria (SFB) in the small intestine during the early post-weaning period. Mice that do not receive maternal SIgA also display elevated T helper type 17 (Th17) cell activation in the intestine, which persists into adulthood and is associated with more severe inflammation in response to the HDM model of asthma. This study demonstrates a mechanism by which breast-milk-derived SIgA influences immune development and asthma susceptibility by modulating the early-life gut microbiota., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Perfluorooctane sulfonic acid (PFOS) is a long-chain per- and polyfluoroalkyl substance (PFAS), a persistent organic pollutant, which has been used in aqueous film-forming foams. Emerging epidemiological evidence indicates a significant body burden of PFOS is observed in the lungs. Furthermore, developmental PFOS exposure dysregulates lung development and exacerbates eosinophilic inflammation, which are critical risk factors for asthma. However, it is unknown whether PFOS exerts sex-dependent effects on house dust mite (HDM) induced asthmatic progression and allergic inflammation. In this study, timed pregnant Balb/cJ dams were dosed orally via PFOS (1.0 mg/kg/d) spiked or vehicle control mealworms from gestational day (GD) 0.5 to postnatal day (PND) 21. Subsequently, HDM (30 μg/day) was administered starting at PND 77-82 for 10 days, and the mice were sacrificed 48 h after their final treatment. The serum and lung PFOS concentrations were 3.391 ± 0.189 μg/mL and 3.567 ± 0.1676 μg/g in the offspring, respectively. Male mice exposed to PFOS + HDM showed higher total cell counts in bronchoalveolar lavage fluid (BALF), macrophage counts, and eosinophil counts compared to mice exposed to HDM alone. Female mice exposed to PFOS + HDM had increased BALF eosinophil percentage, mucous production, alternatively activated (M2) macrophage polarization, and M2-associated gene expression compared to female mice exposed to HDM alone. PFOS exposure had no significant effect on HDM-induced IL-4, IL-5, or IL-13, but RANTES was further elevated in female mice. Overall, our data suggest that developmental PFOS exposure increased the risk of exacerbated eosinophilic inflammation and M2 polarization, which were more severe in female mice, suggesting sex-dependent developmental effects of PFOS on allergic airway responses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this study., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Epidemiological studies have shown that coke oven emissions (COEs) affect the deterioration of asthma, but has not been proven by experimental results. In this study, we found for the first time that COEs exacerbate allergen house dust mite (HDM)-induced allergic asthma in the mouse model. The findings reveal that airway inflammation, airway remodeling and allergic reaction were aggravated in the COE + HDM combined exposure group compared with the individual exposure group. Mechanism studies indicated higher levels of iron and MDA in the COE + HDM combined exposure group, along with increased expression of Ptgs2 and reduced GPX4 expression. Iron chelator deferoxamine (DFO) effectively inhibited ferroptosis induced by COE synergistically with HDM in vitro. Further studies highlighted the role of ferritinophagy in the COE + HDM-induced ferroptosis. 3-methyladenine (3-MA) could inhibit ferroptosis in the COE + HDM exposure group. Interestingly, we injected DFO intraperitoneally into mice in the combined exposure group and found DFO could significantly inhibit the COE-exacerbated ferroptosis and allergic asthma. Our findings link ferroptosis with COE-exacerbated allergic asthma, implying that ferroptosis may have important therapeutic potential for asthma in patients with occupational exposure of COE., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Asthma exhibits a distinct sex bias in the disease prevalence, severity, and response to therapy. However, sex-related differences in alterations of the lung proteome mediated by aeroallergens critical in asthma, such as house dust mites (HDM), remain unknown. In this study, we define sex-related differences in the lung proteome using an HDM-challenged mouse model by 1D LC-MS/MS. Sex-disaggregated data analysis showed that 406 proteins were uniquely altered in females, 273 proteins were uniquely altered in males, and 414 proteins were altered in both females and males in response to HDM. In a linear mixed model analysis, sex modified the HDM exposure effect for 163 proteins, i.e., a significant sex:exposure interaction was identified in 84 proteins in females and 35 proteins in males. Of these, 12 proteins showed a significant sex effect in both female and male lungs. We further selected 3 proteins Tjp1, Lamtor1, and G3BP2 for independent confirmation studies. Our findings detail the sex-specific lung proteome in response to an aeroallergen critical in asthma and demonstrate that sex is a significant effect modifier of HDM response. These results will serve as a valuable resource for delineating sex-specific mechanisms in aeroallergen-driven responses in asthma research.

Background: House dust mite is the most frequent trigger of allergic asthma, with innate and adaptive immune mechanisms playing critical roles in outcomes. We recently identified the nucleotide-binding oligomerisation domain 1 (NOD1)/receptor-interacting serine/threonine protein kinase 2 (RIPK2) signalling pathway as a relevant contributor to murine house dust mite-induced asthma. This study aimed to evaluate the effectiveness of a pharmacological RIPK2 inhibitor administered locally as a preventive and therapeutic approach using a house dust mite-induced asthma model in wild-type and humanised NOD1 mice harbouring an asthma-associated risk allele, and its relevance using air-liquid interface epithelial cultures from asthma patients., Methods: A RIPK2 inhibitor was administered intranasally either preventively or therapeutically in a murine house dust mite-induced asthma model. Airway hyperresponsiveness, bronchoalveolar lavage composition, cytokine/chemokine expression and mucus production were evaluated, as well as the effect of the inhibitor on precision-cut lung slices. Furthermore, the inhibitor was tested on air-liquid interface epithelial cultures from asthma patients and controls., Results: While local preventive administration of the RIPK2 inhibitor reduced airway hyperresponsiveness, eosinophilia, mucus production, T-helper type 2 cytokines and interleukin 33 (IL-33) in wild-type mice, its therapeutic administration failed to reduce the above parameters, except IL-33. By contrast, therapeutic RIPK2 inhibition mitigated all asthma features in humanised NOD1 mice. Results in precision-cut lung slices emphasised an early role of thymic stromal lymphopoietin and IL-33 in the NOD1-dependent response to house dust mite, and a late effect of NOD1 signalling on IL-13 effector response. RIPK2 inhibitor downregulated thymic stromal lymphopoietin and chemokines in house dust mite-stimulated epithelial cultures from asthma patients., Conclusion: These data support that local interference of the NOD1 signalling pathway through RIPK2 inhibition may represent a new therapeutic approach in house dust mite-induced asthma., Competing Interests: Conflict of interest: All authors report support for the present study from Inserm and grants from Institut Pasteur (PTR (18-16)) and ANR (18-CE14-0020). M. Chamaillard reports grants from CoPOC grant entitled RIFFLE from Inserm-Transfert. M. Chamaillard, I. Gomperts Boneca, M. Fanton d'Andon, S. Ait Yahlia, D. Alvarez-Simon and A. Tsicopoulos report a patent filed on 11 October 2023 (Nber EP23306767.7). I. Gomperts Boneca and M. Fanton d'Andon report support for the present study from Laboratoire d'Excellence “Integrative Biology of Emerging Infectious Diseases” (ANR-10-LABX-62-IBEID)., (Copyright ©The authors 2024. For reproduction rights and permissions contact permissions@ersnet.org.)

Atopic dermatitis (AD) is a chronic disease characterized by relapsed eczema and intractable itch, and is often triggered by house dust mites (HDM). PAR2 is a G-protein coupled receptor on keratinocytes and may be activated by HDM to affect AD processes. We first established a HDM-derived AD mouse model in wild-type (WT) and Par2 -/- mice. Single cell RNA sequencing of the diseased skins found a stronger cellular communication between the ligand macrophage migration inhibitory factor (MIF) from keratinocytes and its receptors on antigen-presenting cells, suggesting the critical role of MIF in AD. HDM-WT mice showed severer skin lesions and pathological changes with stronger immunofluorescence MIF signals in skin sections than HDM- Par2 -/- mice. Primary keratinocytes from WT mice stimulated with HDM or SLIGRL (PAR2 agonist) secreted more MIF in cultured medium and induced stronger immunofluorescence MIF signals than those from Par2 -/- mice. The skin section of HDM-WT mice showed higher immunofluorescence signals of P115 (relating to MIF secretion) and KIF13B (possibly relating to intracellular trafficking of MIF) than that of HDM- Par2 -/- mice. Acetylation of α-tubulin increased after stimulation by SLIGRL in WT keratinocytes but not in Par2 -/- keratinocytes. HDM-WT mice treated with the MIF antagonist ISO-1 displayed improvement of AD-like presentations and lower expressions of IL-4, IL-13, TSLP and Arg1 (a biomarker of M2 macrophage) mRNAs. We conclude that MIF is an important cytokine and is significantly increased in the AD model. PAR2 affects AD changes by regulating the expression, intracellular trafficking, and secretion of MIF in epidermis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhou, Zhang, Zhang, Rao, Tang, Wang and Zhao.)

Background and Objectives : Allergy to dust mites (HDMs) plays an important role in atopic dermatitis (AD). However, the role of this allergy in other dermatoses is little known. The aim of this study was to assess hypersensitivity to HDMs in patients with AD or hand disease using the basophil activation test. Material and Methods : A total of 52 patients with AD, 57 with hand eczema disease, and 68 healthy volunteers qualified for this study. Diagnosis was based on the Hanifin and Rajka criteria, dermatological assessment, and exclusion of other dermatoses. The participants underwent skin prick tests (SPTs), a basophil activation test (BAT) with D. pteronyssinus allergen extract, and the concentration of specific IgE (sIgE) for the same allergen in blood serum was determined. Results : Positive results in all tests (SPT, sIgE, and BAT) were obtained (24 (46.2%) patients with AD, 9 (15.8%) with hand disease, and none in the control group for p < 0.05). The results of the SPT, sIgE, and BAT correlated with each other in the AD and hand eczema groups (Spearmen correlation test, r = 0.72 or 0.85, p < 0.05). However, the BAT was positive more often than the SPT and sIgE for D. pteronyssinus. Conclusions : House dust mite hypersensitivity is common in patients with AD and eczema. The BAT may be more sensitive for assessing sensitization to house dust mites, especially in patients with hand eczema.

The ability of air pollution to induce acute exacerbation of asthma is well documented. However, the ability of ozone (O 3 ), the most reactive gaseous component of air pollution, to function as a modulator during sensitization is not well established. C57BL/6 J male mice were intranasally sensitized to house dust mite (HDM) (40 μg/kg) for 3 weeks on alternate days in parallel with once-a-week O 3 exposure (1 ppm). Mice were euthanized 24 h following the last HDM challenge. Lung lavage, histology, lung function (both forced oscillation and forced expiration-based), immune cell profiling, inflammation (pulmonary and systemic), and immunoglobulin production were assessed. Compared to HDM alone, HDM + O 3 leads to a significant increase in peribronchial inflammation (p < 0.01), perivascular inflammation (p < 0.001) and methacholine-provoked large airway hyperreactivity (p < 0.05). Serum total IgG and IgE and HDM-specific IgG1 were 3-5 times greater in HDM + O 3 co-exposure compared to PBS and O 3 -exposed groups. An increase in activated/mature lung total and monocyte-derived dendritic cells (p < 0.05) as well as T-activated, and T memory lymphocyte subset numbers (p < 0.05) were noted in the HDM + O 3 group compared to HDM alone group. Concurrent O 3 inhalation and HDM sensitization also caused significantly greater (p < 0.05) lung tissue interleukin-17 pathway gene expression and mediator levels in the serum. Redox imbalance was manifested by impaired lung antioxidant defense and increased oxidants. O 3 inhalation during allergic sensitization coalesces in generating a significantly worse T H 17 asthmatic phenotype., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Air trapping, often attested in humans by elevated residual volume (RV) and ratio of RV on total lung capacity (RV/TLC), is frequently observed in asthma. Confirming these alterations in experimental asthma would be important for translational purposes. Herein, lung volumes were investigated in a mouse model of pulmonary allergic inflammation., Methods: Eight- to 10-week-old male C57BL/6 and BALB/c mice were exposed once daily to intranasal house dust mite (HDM) for 10 consecutive days. All readouts were measured 24 h after the last exposure. Lung volumes were assessed with the flexiVent using a new automated method consisting of degassing the lungs followed by a full-range pressure-volume maneuver. The weight and the volume of the lungs were also measured ex vivo and a lobe was further processed for histological analyses., Results: HDM exposure led to tissue infiltration with inflammatory cells, goblet cell hyperplasia, thickening of the airway epithelium, and elevated ex vivo lung weight and volume. It also decreased TLC and vital capacity but without affecting RV and RV/TLC. These observations were similar between the two mouse strains., Conclusion: Alterations of lung volumes in a murine model of pulmonary allergic inflammation are inconsistent with observations made in human asthma. These discrepancies reflect the different means whereby lung volumes are measured between species. The invasive method used herein enables RV to be measured more precisely and without the confounding effect of air trapping, suggesting that changes in RV and RV/TLC using this method in mice should be interpreted differently than in humans., (© 2024. The Author(s).)

Background: Trained immunity results in long-term immunological memory, provoking a faster and greater immune response when innate immune cells encounter a secondary, often heterologous, stimulus. We have previously shown that house dust mite (HDM)-induced innate training is amplified in mice expressing the human macrophage migration inhibitory factor (MIF) CATT 7 functional polymorphism., Aim: This study investigated the ability of mesenchymal stromal cells (MSCs) to modulate MIF-driven trained immunity both in vitro and in vivo., Methods: Compared with wild-type mice, in vivo HDM-primed bone marrow-derived macrophages (BMDMs) from CATT 7 mice expressed significantly higher levels of M1-associated genes following lipopolysaccharide stimulation ex vivo. Co-cultures of CATT 7 BMDMs with MSCs suppressed this HDM-primed effect, with tumor necrosis factor alpha (TNF-α) being significantly decreased in a cyclooxygenase 2 (COX-2)-dependent manner. Interestingly, interleukin 6 (IL-6) was suppressed by MSCs independently of COX-2. In an in vitro training assay, MSCs significantly abrogated the enhanced production of pro-inflammatory cytokines by HDM-trained CATT 7 BMDMs when co-cultured at the time of HDM stimulus on day 0, displaying their therapeutic efficacy in modulating an overzealous human MIF-dependent immune response. Utilizing an in vivo model of HDM-induced trained immunity, MSCs administered systemically on day 10 and day 11 suppressed this trained phenomenon by significantly reducing TNF-α and reducing IL-6 and C-C motif chemokine ligand 17 (CCL17) production., Conclusions: This novel study elucidates how MSCs can attenuate an MIF-driven, HDM-trained response in CATT 7 mice in a model of allergic airway inflammation., Competing Interests: Declaration of Competing Interest The authors have no commercial, proprietary or financial interest in the products or companies described in this article., (Copyright © 2024 International Society for Cell & Gene Therapy. All rights reserved.)

Background and Purpose: Airway epithelial cells (AECs) regulate the activation of epithelial-mesenchymal trophic units (EMTUs) during airway remodelling through secretion of signalling mediators. However, the major trigger and the intrinsic pathogenesis of airway remodelling is still obscure., Experimental Approach: The differing expressed genes in airway epithelia related to airway remodelling were screened and verified by RNA-sequencing and signalling pathway analysis. Then, the effects of increased cathepsin K (CTSK) in airway epithelia on airway remodelling and EMTU activation were identified both in vitro and in vivo, and the molecular mechanism was elucidated in the EMTU model. The potential of CTSK as an an effective biomarker of airway remodelling was analysed in an asthma cohort of differing severity. Finally, an inhibitor of CTSK was administered for potential therapeutic intervention for airway remodelling in asthma., Key Results: The expression of CTSK in airway epithelia increased significantly along with the development of airway remodelling in a house dust mite (HDM)-stressed asthma model. Increased secretion of CTSK from airway epithelia induced the activation of EMTUs by activation of the PAR2-mediated pathway. Blockade of CTSK inhibited EMTU activation and alleviated airway remodelling as an effective intervention target of airway remodelling., Conclusion and Implications: Increased expression of CTSK in airway epithelia is involved in the development of airway remodelling in asthma through EMTU activation, mediated partly through the PAR2-mediated signalling pathway. CTSK is a potential biomarker for airway remodelling, and may also be a useful intervention target for airway remodelling in asthma patients., (© 2024 British Pharmacological Society.)

The objective of the study was to evaluate the effect of photobiomodulation (PBM) with laser on the inflammatory process in an experimental in vitro model of ACO. The groups were: (1) human bronchial epithelial cells (BEAS-2B); (2) BEAS-2B cells treated with dexamethasone; (3) BEAS-2B cells irradiated with laser; (4) BEAS-2B cells stimulated with cigarette smoke extract (CSE) + House Dust Mite (HDM); (5) BEAS-2B cells stimulated with CSE + HDM and treated with dexamethasone; (6) BEAS-2B cells incubated with CSE + HDM and irradiated with laser. After 24 h, cytokines were quantified. There was a reduction in TNF-α, IL-1β, IL-6, IL-4, IL-5, IL-13, IL-17, IL-21, IL-23, and an increase in IL-10 and IFN-γ in cells from the laser-irradiated ACO group compared to only ACO group. With these results, we can suggest that photobiomodulation acts in the modulation of inflammation observed in ACO, and may be a treatment option., (© 2024 Wiley‐VCH GmbH.)

Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by the accumulation of amyloid-β (Aβ) plaques, neuroinflammation, and neuronal death. Besides aging, various comorbidities increase the risk of AD, including obesity, diabetes, and allergic asthma. Epidemiological studies have reported a 2.17-fold higher risk of dementia in asthmatic patients. However, the molecular mechanism(s) underlying this asthma-associated AD exacerbation is unknown. This study was designed to explore house dust mite (HDM)-induced asthma effects on AD-related brain changes using the App NL-G-F transgenic mouse model of disease. Male and female 8-9 months old C57BL/6J wild type and App NL-G-F mice were exposed to no treatment, saline sham, or HDM extract every alternate day for 16 weeks for comparison across genotypes and treatment. Mice were euthanized at the end of the experiment, and broncho-alveolar lavage fluid (BALF), blood, lungs, and brains were collected. BALF was used to quantify immune cell phenotype, cytokine levels, total protein content, lactate dehydrogenase (LDH) activity, and total IgE. Lungs were sectioned and stained with hematoxylin and eosin, Alcian blue, and Masson's trichrome. Serum levels of cytokines and soluble Aβ1-40/42 were quantified. Brains were sectioned and immunostained for Aβ, GFAP, CD68, and collagen IV. Finally, frozen hippocampi and temporal cortices were used to perform Aβ ELISAs and cytokine arrays, respectively. HDM exposure led to increased levels of inflammatory cells, cytokines, total protein content, LDH activity, and total IgE in the BALF, as well as increased pulmonary mucus and collagen staining in both sexes and genotypes. Levels of serum cytokines increased in all HDM-exposed groups. Serum from the App NL-G-F HDM-induced asthma group also had significantly increased soluble Aβ1-42 levels in both sexes. In agreement with this peripheral change, hippocampi from asthma-induced male and female App NL-G-F mice demonstrated elevated Aβ plaque load and increased soluble Aβ 1-40/42 and insoluble Aβ 1-40 levels. HDM exposure also increased astrogliosis and microgliosis in both sexes of App NL-G-F mice, as indicated by GFAP and CD68 immunoreactivity, respectively. Additionally, HDM exposure elevated cortical levels of several cytokines in both sexes and genotypes. Finally, HDM-exposed groups also showed a disturbed blood-brain-barrier (BBB) integrity in the hippocampus of App NL-G-F mice, as indicated by decreased collagen IV immunoreactivity. HDM exposure was responsible for an asthma-like condition in the lungs that exacerbated Aβ pathology, astrogliosis, microgliosis, and cytokine changes in the brains of male and female App NL-G-F mice that correlated with reduced BBB integrity. Defining mechanisms of asthma effects on the brain may identify novel therapeutic targets for asthma and AD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Tripartite motif (Trim) 31 is important for numerous inflammatory diseases. However, whether Trim31 regulates airway inflammation in asthma remains undetermined. The present work explored the role of Trim31 in airway inflammation in asthmatic mice established by ovalbumin (OVA) stimulation. Trim31 expression was markedly downregulated in the lungs of asthmatic mice. Compared with wild-type (WT) mice, Trim31 -/- mice showed more severe pathological changes accompanied by increased inflammatory cell infiltration after OVA induction. House dust mite (HDM) stimulation evoked airway epithelial cell injury and inflammation, which were exacerbated by Trim31 silencing or attenuated by Trim31 overexpression. Further examination revealed that Trim31 deficiency exacerbated the activation of the NLRP3 inflammasome in OVA-induced asthmatic mice and HDM-stimulated airway epithelial cells. The inhibition of NLRP3 markedly diminished the Trim31 silencing-mediated enhancement of HDM-induced injury and inflammation in airway epithelial cells. In conclusion, this work demonstrates that Trim31 acts as a crucial mediator of airway inflammation in asthma. Trim31 deficiency may contribute to the progression of asthma by increasing NLRP3 inflammasome activation, suggesting that Trim31 is a potential therapeutic target for asthma., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Airway epithelial barrier dysfunction has been proved to contribute to the development of type 2 inflammation of asthma. Interleukin (IL)-37 is a negative regulator of immune responses and allergic airway inflammation. However, whether IL-37 has any effect on airway epithelial barrier has been unknown., Methods: We evaluated the role of IL-37 in both mouse model and cultured 16HBE cells. Histology and ELISA assays were used to evaluate airway inflammation. FITC-dextran permeability assay was used to evaluate the airway epithelial barrier function. Immunofluorescence, western blot and quantitative Real-Time PCR (RT-PCR) were used to evaluate the distribution and expression of tight junction proteins. RT-PCR and Ca 2+ fluorescence measurement were used to evaluate the mRNA expression and activity of store-operated calcium entry (SOCE)., Results: IL-37 inhibited house dust mite (HDM)-induced airway inflammation and decreased the levels of IgE in serum and type 2 cytokines in bronchoalveolar lavage fluid (BALF) compared to asthmatic mice. IL-37 protected against HDM-induced airway epithelial barrier dysfunction, including reduced leakage of FITC-dextran, enhanced expression of TJ proteins, and restored the membrane distribution of TJ proteins. Moreover, IL-37 decreased the level of IL-33 in the BALF of asthmatic mice and the supernatants of HDM-treated 16HBE cells. IL-37 decreased the peak level of Ca 2+ fluorescence induced by thapsigargin and HDM, and inhibited the mRNA expression of Orai1, suggesting an inhibiting effect of IL-37 on SOCE in airway epithelial cells., Conclusion: IL-37 plays a protective role in airway inflammation and HDM-induced airway epithelial barrier dysfunction by inhibiting SOCE., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Immune memory has been expanded to group 2 innate lymphoid cells (ILC2s), but the cellular and molecular bases remain incompletely understood. Based on house dust mite (HDM)-induced mice asthma models and human samples, we applied flow cytometry, parabiosis, in vivo imaging and adoptive transplantation to confirm the persistence, migration and function of CD45 + lineage - CD90.2 + NK1.1 - NKp46 - ST2 - KLRG1 + IL-17RB + memory-like ILC2s (ml-ILC2s). Regulated by CCR9/CCL25 and S1P signaling, ml-ILC2s reside in the lamina propria of small intestines (siLP) in asthma remission, and subsequently move to airway upon re-encountering antigens or alarmins. Furthermore, ml-ILC2s possess properties of longevity, potential of rapid proliferation and producing IL-13, and display transcriptional characteristics with up-regulation of Tox and Tcf-7. ml-ILC2s transplantation restore the asthmatic changes abrogated by Tox and Tcf7 knockdown. Our data identify siLP ml-ILC2s as a memory-like subset, which promotes asthma relapse. Targeting TCF-1 and TOX might be promising for preventing asthma recurrence., (© 2024. The Author(s).)

As the relationship between the gut microbiome and allergies becomes better understood, targeted strategies to prevent and treat allergies through gut microbiome modulation are being increasingly developed. In the study presented herein, we screened various probiotics for their ability to inhibit mast cell degranulation and identified Lactiplatibacillus plantarum HD02 and MD159 as effective candidates. The two strains significantly attenuated vascular permeability induced by mast cell degranulation in a passive cutaneous anaphylaxis (PCA) model and, in the MC903-induced murine atopic dermatitis (AD) model, demonstrated comparable preventive effects against allergies, reducing blood levels of MCPT-1 (mast cell protease-1) and total IgE. In the house dust mite (HDM)-induced murine AD model, both L. plantarum HD02 and MD159 showed therapeutic effects, with L. plantarum HD02 demonstrating superior efficacy. Nevertheless, L. plantarum MD159 better suppressed transepidermal water loss (TEWL). Furthermore, L. plantarum HD02 and MD159 significantly increased the number of splenic Foxp3 + regulatory T cells, with L. plantarum MD159 having a more pronounced effect. However, only L. plantarum HD02 achieved a reduction in immune cells in the draining lymph nodes. Our findings highlight L. plantarum HD02 and MD159 as promising candidates for the prevention and treatment of allergies, demonstrating significant efficacy in suppressing mast cell degranulation, reducing the number of allergy biomarkers, and modulating immune responses in experimental models of AD. Their distinct mechanisms of action suggest potential complementary roles in addressing allergic diseases, underscoring their therapeutic promise in clinical applications.

Background: Allergen-specific immunotherapy, a unique inducer of tolerance, may result in T cell exhaution., Aims: To investigate how the duration of house dust mite (HDM) subcutaneous immunotherapy (SCIT) affects the expression of major immune checkpoint (ICP) molecules on the surface of CD4 + T-helper and regulatory T (Treg) cells., Study Design: Cross-sectional study., Methods: We enrolled 28 children with HDM-induced allergic rhinitis (AR) and six controls. The study participants were divided into six groups: one group each of patients in their first, second, and third years of HDM-SCIT; one group each comprising those in the first year following HDM-SCIT and those on pharmacotherapy; and the control group. The expression of ICPs on CD4 + T and Treg cells was determined using flow cytometry, and plasma levels of soluble ICPs were estimated by ELISA., Results: Our results revealed a significant increase in the expression of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and lymphocyte activation gene 3 (LAG-3) on CD4 + T cells during the second and third years of SCIT, respectively. Additionally, a strong correlation was observed between the expression of CTLA-4 and T cell immunoglobulin and mucin domain containing molecule-3 in CD4 + T cells. Furthermore, we observed a significant correlation between the expressions of programmed cell death protein-1, CTLA-4, T cell Immunoreceptor with Immunoglobulin and Immunoreceptor Tyrosine-Based Inhibitory Motif domain, and LAG-3 on both CD4 + T and Treg cells. A robust correlation was observed between the plasma levels of soluble ICPs., Conclusion: HDM-SCIT induces CD4 + T cell exhaution, which may contribute to tolerance induction in children with AR., Competing Interests: Conflict of Interest: The authors declare that they have no conflict of interest.

Background: Previous house dust mite subcutaneous immunotherapy (HDM SCIT) placebo-controlled trials have small sample sizes and lack a consensus on baseline treatment., Objective: To determine the efficacy of HDM SCIT in moderate-to-severe allergic rhinitis (AR) patients treated with an intranasal corticosteroid at baseline., Methods: We conducted a randomized, placebo-controlled trial comparing HDM SCIT against placebo in Dermatophagoides pteronyssinus (Der p) sensitized. All patients received standard of care according to Allergic Rhinitis and its Impact on Asthma (ARIA) guideline, including an intranasal steroid (INCS) at baseline. The primary endpoint was the comparison of a composite score, combining the total nasal symptom score and medication score, assessed at the twelfth month post-treatment., Results: Of the 144 subjects, 108 received HDM-SCIT and 36 received a placebo. The median age was 30 years (range 11-61), with 60% being female. The mean Der p wheal diameter was 9.4 mm (SD 4.4). After one year of treatment, the composite score median (IQR) in the HDM SCIT group and the placebo group was 0.75 (0.50-1.13) and 0.63 (0.50-1.25), respectively (p > 0.05). Both groups exhibited a significant mean change in the composite score from baseline (p < 0.001), but there was no significant difference between the groups. The median (IQR) serum Der p-specific immunoglobulin G4 level significantly increased only in the HDM SCIT arm (p ≤ 0.001)., Conclusion: One-year HDM SCIT significantly reduced both symptoms and medication use in HDM-allergic rhinitis patients. However, the changes were not significantly different from those in the placebo group, who also received an INCS at baseline. A longer-term study is warranted to assess disease modification factors.

Purpose: This prospective study aims to provide further supportive evidence by assessing the sustained effectiveness and safety of sublingual immunotherapy (SLIT) using a vaccine containing house dust mite (HDM) extracts in patients diagnosed with allergic rhinitis (AR) with/without conjunctivitis (AR/C)., Materials and Methods: AR/C patients (n = 111, SLIT group: 57, control group: 54) allergic to HDM were treated with standardized SLIT drops or symptomatic drugs from October to December in 2020. The patients were directed by the investigators to attend annual hospital visits for the assessment of various parameters including the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), visual analog scale (VAS), total nasal symptom score (TNSS), total ocular symptom score (TOSS) and total medication score (TMS). During the study period, all participants were mandated to maintain comprehensive records of any adverse events (AEs) on diary cards, which were then communicated to the investigators via telephone., Results: At baseline (2020), TNSS, TOSS, TMS, VAS, and RQLQ scores were comparable between SLIT and control groups (P > 0.05). After one year of treatment (2021), significant reduction in all scores compared to the baseline for both groups (P < 0.001). At the end of the second year of treatment (2022), TNSS and RQLQ score in the SLIT group continued to decrease significantly compared to 2021 (P < 0.05). In the third year (2023), the control group showed a rebound in TNSS, TOSS, TMS, and RQLQ scores, significant differences compared to 2022 or 2021 (P < 0.05). Besides, the SLIT group had significantly lower scores across all domains of RQLQ compared to the control group (P < 0.001). Symptomatic treatment influenced the scores of Nasal Symptoms, Eye Symptoms, Practical Problems, and Emotions domains significantly in 2023 compared to 2021 or 2022 (P < 0.05). Within the SLIT group, no significant differences in TNSS, TMS, VAS, and RQLQ scores were observed between monosensitized and polysensitized patients throughout the three years of treatment (P > 0.05). All AEs were mild to moderate., Conclusion: The 3-year course of HDM-SLIT has shown significant therapeutic efficacy and a favorable safety profile in patients with AR/C. Importantly, our study presents initial evidence suggesting that the greater impact of AR/C on quality of life (QoL) may primarily stem from nasal symptoms, eye symptoms, practical issues, and emotional well-being., Competing Interests: Declaration of competing interest All authors declare no financial or commercial conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

House dust mite (HDM) is the most significant indoor allergen, responsible for not only many cases of rhinoconjunctivitis but also for many cases of bronchial asthma, rendering it of considerable socioeconomic relevance. Besides symptomatic treatment and avoidance measures, allergen immunotherapy (AIT) is crucial, as the only causal, disease-modifying therapeutic approach. However, high diagnostic certainty is essential for initiating AIT. The challenge in making a correct diagnosis lies in interpreting the demonstrated HDM sensitization regarding its clinical relevance (clinically silent sensitization vs. allergy). While the risk of allergy increases with the level of IgE titers against HDM extract, Der p 1, or Der p 2, as well as with the breadth of the molecular sensitization profile against HDM components (Der p 1, Der p 2, Der p 23), no threshold can be defined for the presence of allergy, nor can sensitization to a specific component be confidently considered allergy inducing. It should be noted that at least in Southern Bavaria, the prevalence of Der p 23 sensitization is too low to be considered a major allergen, and Der p 23 is not able to molecularly differentiate all HDM sensitizations when added to the two major allergens Der p 1 and Der p 2. Evidently, HDM possesses a diverse profile of allergens, with some relevant ones possibly yet to be described. Unfortunately, patient history does not provide a sufficient assessment of the clinical relevance of a demonstrated HDM sensitization, necessitating allergen provocation testing before initiating AIT with HDM, despite the relatively large effort involved., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: The integrity of the airway epithelium is guarded by the airway basal cells that serve as progenitor cells and restore wounds in case of injury. Basal cells are a heterogenous population, and specific changes in their behavior are associated with chronic barrier disruption-mechanisms that have not been studied in detail in allergic rhinitis (AR)., Objective: We aimed to study basal cell subtypes in AR and healthy controls., Methods: Single-cell RNA sequencing (scRNA-Seq) of the nasal epithelium was performed on nonallergic and house dust mite-allergic AR patients to reveal basal cell diversity and to identify allergy-related alterations. Flow cytometry, immunofluorescence staining, and in vitro experiments using primary basal cells were performed to confirm phenotypic findings at the protein level and functionally., Results: The scRNA-Seq, flow cytometry, and immunofluorescence staining revealed that basal cells are abundantly and heterogeneously present in the nasal epithelium, suggesting specialized subtypes. The total basal cell fraction within the epithelium in AR is increased compared to controls. scRNA-Seq demonstrated that potentially beneficial basal cells are missing in AR epithelium, while an activated population of allergy-associated basal cells is more dominantly present. Furthermore, our in vitro proliferation, wound healing assay and air-liquid interface cultures show that AR-associated basal cells have altered progenitor capacity compared to nonallergic basal cells., Conclusions: The nasal basal cell population is abundant and diverse, and it shifts toward a diseased state in AR. The absence of potentially protective subtypes and the rise of a proinflammatory population suggest that basal cells are important players in maintaining epithelial barrier defects in AR., Competing Interests: Disclosure statement The author’s laboratories are supported by grants from the research council of the KU Leuven (C14/18/086). T.W. is supported by a predoctoral grant of the Fund for Scientific Research Flanders (FWO), Belgium (11L8922N). B.S. received a postdoctoral fellowship from the Fund for Scientific Research Flanders (FWO), Belgium (12U6721N). K.M. received a junior postdoctoral fellowship from the Fund for Scientific Research Flanders (FWO), Belgium (12Z0622N). D.M.A.B. is a recipient of a senior clinical investigator grant of the Fund for Scientific Research Flanders (FWO), Belgium (1801014N) and from the Bijzonder Onderzoeksfonds—fundamenteel klinisch mandaat (BOF-FKM) of the KU Leuven (FKO CM23-FKO-02). Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Atopic dermatitis (AD) is the most common chronic inflammatory skin disease. Allergen-specific immunotherapy is a treatment option for selected patients with severe AD sensitization to house dust mites (HDM)., Objective: To report the first case of successful treatment with HDM sublingual immunotherapy (SLIT) tablets in patients with severe AD., Methods: A Thai male patient with HDM sensitization and severe AD who had not responded to topical corticosteroids and calcineurin inhibitors underwent 1 month of HDM subcutaneous immunotherapy (SCIT), after which his skin symptoms were minimally improved. He lost follow-up SCIT and the symptoms worsened, with large wheal lesions appearing at the SCIT injection site, so we decided to switch from SCIT to HDM SLIT tablets., Results: After the SLIT treatment, the AD and skin lesions improved and the medication could be stopped., Conclusions: HDM SLIT might be an alternative treatment in patients with HDM sensitization and severe AD who are refractory to conventional treatment.

Background: It is reported that CD123 + HLA-DR- cells in PBMC are basophils, and CD203c, CD63, and FcεRI molecules are activation markers of basophils. However, little is known of CD123 + HLA-DR-cells in blood granulocytes., Objective: To investigate the presence of CD123 + HLA-DR- cells in the blood granulocytes and peripheral PBMC of patients with allergic rhinitis (AR), as well as the impact of allergens on the cell membrane markers of basophils., Methods: Flow cytometry was used to detect the expression of the membrane molecules., Results: While CD123 + HLA-DR- PBMCs are representative of basophils, their presence did not significantly change in patients with AR. In contrast, both the percentage and number of CD123 + HLA-DR- granulocytes, which make up only up to 50% of basophils, were significantly increased in patients with seasonal (sAR) and perennial AR (pAR). CD63+, CD203c+, and FcεRIα+ cells within CD123 + HLA-DR- granulocytes also showed enhanced activity in patients with AR. Allergen extracts from house dust mite allergen extract (HDME) and Artemisia sieversiana wild extract further increased the number of CD123 + HLA-DR- cells in granulocytes of sAR and pAR patients, as well as in PBMCs of pAR patients., Conclusions: The use of CD123 + HLA-DR- granulocytes and PBMC may not be sufficient for diagnosing AR. Allergens could potentially contribute to the development of AR by influencing the number of CD123 + HLA-DR- cells, as well as the expression of CD63, CD203c, and FcεRIαin these cells.

Dendritic cells (DCs) are pivotal in regulating allergic asthma. Our research has shown that the absence of Sema3E worsens asthma symptoms in acute and chronic asthma models. However, the specific role of PlexinD1 in these processes, particularly in DCs, remains unclear. This study investigates the role of PlexinD1 in CD11c+ DCs using a house dust mite (HDM) model of asthma. We generated CD11c+ DC-specific PlexinD1 knockout (CD11cPLXND1 KO) mice and subjected them, alongside wild-type controls (PLXND1fl/fl), to an HDM allergen protocol. Airway hyperresponsiveness (AHR) was measured using FlexiVent, and immune cell populations were analyzed via flow cytometry. Cytokine levels and immunoglobulin concentrations were assessed using mesoscale and ELISA, while collagen deposition and mucus production were examined through Sirius-red and periodic acid Schiff (PAS) staining respectively. Our results indicate that CD11cPLXND1 KO mice exhibit significantly exacerbated AHR, characterized by increased airway resistance and tissue elastance. Enhanced mucus production and collagen gene expression were observed in these mice compared to wild-type counterparts. Flow cytometry revealed higher CD11c+ MHCIIhigh CD11b+ cell recruitment into the lungs, and elevated total and HDM-specific serum IgE levels in CD11cPLXND1 KO mice. Mechanistically, co-cultures of B cells with DCs from CD11cPLXND1 KO mice showed significantly increased IgE production compared to wild-type mice.These findings highlight the critical regulatory role of the plexinD1 signaling pathway in CD11c+ DCs in modulating asthma features., Competing Interests: The authors have no financial conflicts of interest., (Copyright: © 2024 Shan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Allergic asthma is characterized by increased type 2 inflammation, including eosinophils. Subjects with allergic asthma have recurrent symptoms due to their constant exposure to environmental allergens, such as house dust mite (HDM), which can be further exacerbated by respiratory infections like rhinovirus. The immunoproteasome (IP) is a proteolytic machinery that is induced by inflammatory mediators during virus infection, but the role of the IP in airway allergic inflammation during rhinovirus infection remains unknown. Wild-type (WT) and IP knockout (KO) mice were challenged with HDM. At 48 h after the last HDM challenge, mice were infected with rhinovirus 1B (RV-A1B) for 24 h. After HDM and RV-A1B treatment, IP KO (vs. WT) mice had significantly more lung eosinophils and neutrophils, as well as a significantly higher viral load, but less IFN-beta expression, compared to WT mice. A TLR3 agonist polyinosinic-polycytidylic acid (Poly I:C) treatment after RV-A1B infection in HDM-challenged IP KO mice significantly increased IFN-beta expression and reduced viral load, with a minimal effect on the number of inflammatory cells. Our data suggest that immunoproteasome is an important mechanism functioning to prevent excessive inflammation and viral infection in allergen-exposed mice, and that Poly I:C could be therapeutically effective in enhancing the antiviral response and lessening the viral burden in lungs with IP deficiency., Competing Interests: The authors declare no conflicts of interest.

The topic of ragweed pollen (RW) versus house dust mites (HDMs) has often been deliberated, but the increasing incidence of co-sensitization between them has been scarcely addressed. Utilizing Sprague Dawley rats, we explored the effects of co-sensitization with the combination of HDMs and RW pollen extracts in correlation with high-fructose diet (HFrD) by in vitro tracheal reactivity analysis in isolated organ bath and biological explorations. Our findings unveiled interrelated connections between allergic asthma, dyslipidemia, and HFrD-induced obesity, shedding light on their compounding role through inflammation. The increased CRP values and airway hyperresponsiveness to the methacholine challenge suggest a synergistic effect of obesity on amplifying the existing inflammation induced by asthma. One of the major outcomes is that the co-sensitization to HDMs and RW pollen led to the development of a severe allergic asthma phenotype in rats, especially in those with HFrD. Therefore, the co-sensitization to these allergens as well as the HFrD may play a crucial role in the modulation of systemic inflammation, obesity, and airway reactivity.

Antibiotic use in early life disrupts microbial colonization and increases the risk of developing allergies and asthma. We report that mice given antibiotics in early life (EL-Abx), but not in adulthood, were more susceptible to house dust mite (HDM)-induced allergic airway inflammation. This susceptibility was maintained even after normalization of the gut microbiome. EL-Abx decreased systemic levels of indole-3-propionic acid (IPA), which induced long-term changes to cellular stress, metabolism, and mitochondrial respiration in the lung epithelium. IPA reduced mitochondrial respiration and superoxide production and altered chemokine and cytokine production. Consequently, early-life IPA supplementation protected EL-Abx mice against exacerbated HDM-induced allergic airway inflammation in adulthood. These results reveal a mechanism through which EL-Abx can predispose the lung to allergic airway inflammation and highlight a possible preventative approach to mitigate the detrimental consequences of EL-Abx., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Asthma is a heterogeneous, inflammatory disease with several phenotypes and endotypes. Severe asthmatics often exhibit mixed granulocytosis with reduced corticosteroid sensitivity. Bronchom is a newly developed Ayurvedic prescription medicine, indicated for the treatment of obstructive airway disorders. The purpose of the present study was to evaluate the in-vivo efficacy of Bronchom in mouse model of mixed granulocytic asthma with steroidal recalcitrance., Methods: High-performance thin layer chromatography (HPTLC) and Ultra-high performance liquid chromatography (UHPLC) were employed to identify and quantitate the phytometabolites present in Bronchom. The preclinical effectiveness of Bronchom was assessed in house dust mite (HDM) and Complete Freund's adjuvant (CFA)-induced mixed granulocytic asthma model in mice. High dose of dexamethasone was tested parallelly. Specific-pathogen-free C57BL/6 mice were immunized with HDM and CFA and nineteen days later, they were intranasally challenged with HDM for four consecutive days. Then the mice were challenged with nebulized methacholine to evaluate airway hyperresponsiveness (AHR). Inflammatory cell influx was enumerated in the bronchoalveolar lavage fluid (BALF) followed by lung histology. Additionally, the concentrations of Th2 and pro-inflammatory cytokines was assessed in the BALF by multiplexed immune assay. The mRNA expression of pro-inflammatory cytokines and Mucin 5AC (MUC5AC) was also evaluated in the lung., Results: HPTLC fingerprinting and UHPLC quantification of Bronchom revealed the presence of bioactive phytometabolites, namely, rosmarinic acid, gallic acid, methyl gallate, piperine, eugenol and glycyrrhizin. Bronchom effectively reduced AHR driven by HDM-CFA and the influx of total leukocytes, eosinophils and neutrophils in the BALF. In addition, Bronchom inhibited the infiltration of inflammatory cells in the lung as well as goblet cell metaplasia. Further, it also suppressed the elevated levels of Th2 cytokines and pro-inflammatory cytokines in the BALF. Similarly, Bronchom also regulated the mRNA expression of pro-inflammatory cytokines as well as MUC5AC in mice lungs. Reduced effectiveness of a high dose of the steroid, dexamethasone was observed in the model., Conclusions: We have demonstrated for the first time the robust pharmacological effects of an herbo-mineral medicine in an animal model of mixed granulocytic asthma induced by HDM and CFA. The outcomes suggest the potential utility of Bronchom in severe asthmatics with a mixed granulocytic phenotype., (© 2024. The Author(s).)

Allergic rhinitis (AR) is a series of allergic reactions to allergens in the nasal mucosa and is one of the most common allergic diseases that affect both children and adults. Shi-Bi-Lin (SBL) is the modified formula of Cang Er Zi San (CEZS), a traditional Chinese herbal formula used for treating AR. Our study aims to elucidate the anti-inflammatory effects and mechanisms of SBL in house dust mite-induced AR by regulating gut microflora metabolism. In vivo studies showed that nasal allergies and the infiltration of inflammatory cells in the nasal epithelium were significantly suppressed by SBL. Moreover, SBL restored the impaired nasal epithelial barrier function with an increased tight junction protein expression and reduced the endothelial nitric oxide synthase (eNOS). Interestingly, SBL significantly reconstituted the abundance and composition of gut microbiota in AR mice; it increased the relative abundance of potentially beneficial genera and decreased the relative abundance of harmful genera. SBL also restored immune-related metabolisms, which were significantly increased and correlated with suppressing inflammatory cytokines. Furthermore, a network analysis and molecular docking indicated IL-6 was a possible target drug candidate for the SBL treatment. SBL dramatically reduced the IL-6 level in the nasal lavage fluid (NALF), suppressing the IL-6 downstream Erk1/2 and AKT/PI3K signaling pathways. In conclusion, our study integrates 16S rRNA sequencing, microflora metabolism, and network pharmacology to explain the immune mechanism of SBL in alleviating HDM-induced allergic rhinitis.

Background: COVID-19 is a new infectious disease. To investigate whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection increases the adverse reactions of subcutaneous specific immunotherapy (SCIT) in children., Methods: This study was conducted by collecting relevant data from children who underwent house dust mite SCIT from April 3, 2021, to March 18, 2023, including information on the time of COVID-19 infection, symptoms, and adverse reactions after each allergen injection. A mixed effects model was used to analyze the changes in adverse reactions before and after the COVID-19 infection., Results: Among the records of adverse reactions from 2658 injections in 123 children who underwent SCIT, the overall adverse reaction rate before COVID-19 infection was 39.8% and 30.0% after COVID-19 infection. Compared with pre-infection with COVID-19, the risks of overall adverse reactions, local adverse reactions, and systemic adverse reactions of immunotherapy after COVID-19 infection were reduced (odds ratio [OR] = 0.24, 0.31, and 0.28, all P < 0.05). Among the local adverse reactions, the incidence of the unvaccinated group was the highest (15.3% vs. 7.1%). The incidence of overall and local adverse reactions to SCIT decreased in 2-vaccinated COVID-19 recipients (OR = 0.29-0.31, P < 0.05)., Conclusions: In children, SARS-CoV-2 infection does not increase the incidence of adverse reactions to SCIT. This finding can provide a basis for the implementation of allergen-specific immunotherapy (AIT) during the COVID-19 pandemic., (© 2024. The Author(s).)

Interleukin (IL)-9 is present in atopic dermatitis (AD) lesions and is considered to be mainly produced by skin-homing T cells expressing the cutaneous lymphocyte-associated antigen (CLA). However, its induction by AD-associated triggers remains unexplored. Circulating skin-tropic CLA + and extracutaneous/systemic CLA - memory T cells cocultured with autologous lesional epidermal cells from AD patients were activated with house dust mite (HDM) and staphylococcal enterotoxin B (SEB). Levels of AD-related mediators in response to both stimuli were measured in supernatants, and the cytokine response was associated with different clinical characteristics. Both HDM and SEB triggered heterogeneous IL-9 production by CLA + and CLA - T cells in a clinically homogenous group of AD patients, which enabled patient stratification into IL-9 producers and non-producers, with the former group exhibiting heightened HDM-specific and total IgE levels. Upon allergen exposure, IL-9 production depended on the contribution of epidermal cells and class II-mediated presentation; it was the greatest cytokine produced and correlated with HDM-specific IgE levels, whereas SEB mildly induced its release. This study demonstrates that both skin-tropic and extracutaneous memory T cells produce IL-9 and suggests that the degree of allergen sensitization reflects the varied IL-9 responses in vitro, which may allow for patient stratification in a clinically homogenous population.

Exposure to storage mite (SM) and house dust mite (HDM) allergens is a risk factor for sensitization and asthma development; however, the related immune responses and their pathology have not been fully investigated. The HDMs Dermatophagoides farinae and Dermatophagoides pteronyssinus and SM Tyrophagus putrescentiae are potent allergens that induce asthma. Most SM-related studies have focused on the allergic reactions of individuals by measuring their immunoglobulin (Ig)E expression. Considering the limited research on this topic, the present study aims to investigate the differences in the immune responses induced by HDMs and SMs and histologically analyze lung tissues in a mouse asthma model to understand the differential effects of HDM and SM. The results revealed that all mite species induced airway inflammation. Mice challenged with T. putrescentiae had the highest airway resistance and total cell, eosinophil, and neutrophil counts in the bronchoalveolar lavage fluid (BALF). The SM-sensitized groups showed more severe lesions and mucus hypersecretions than the HDM-sensitized groups. Although the degree of HDM and SM exposure was the same, the damage to the respiratory lung tissue was more severe in SM-exposed mice, which resulted in excessive mucin secretion and increased fibrosis. Furthermore, these findings suggest that SM sensitization induces a more significant hypersensitivity response in mucosal immunity than HDM sensitization in asthma models.

Background: Subcutaneous immunotherapy (SCIT) can induce systemic reactions (SRs) in certain patients, but the underlying mechanisms remain to be fully elucidated., Methods: AR patients who were undergoing standardized HDM SCIT (Alutard, ALK) between 2018 and 2022 were screened. Those who experienced two consecutive SRs were included in the study group. A control group was established, matched 1:1 by gender, age, and disease duration with the study group, who did not experience SRs during SCIT. Clinical and immunological parameters were recorded and analyzed both before SCIT and after 1 year of treatment., Results: A total of 161 patients were included, with 79 (49.07%) in the study group. The study group had a higher proportion of AR combined asthma (26.8% vs. 51.8%, p < 0.001) and higher levels of sIgE to HDM and HDM components (all p < .001). Serum IL-4 and IL-13 levels in the study group were higher than those in the control group (p < .05). The study group received a lower maintenance dosage of HDM extracts injections than control group due to SRs (50000SQ vs. 100000SQ, p < .05). After 1 year of SCIT, the VAS score, the lung function parameters of asthmatic patients over 14 years old significantly improved in both groups (all p < .05). After a 7-day exposure to 20 μg/mL HDM extracts, the percentages of Th1, Th17, Tfh10, and Th17.1 in PBMCs decreased, while the Tfh13 cells significantly increased in the study group (p < .05)., Conclusion: The type 2 inflammatory response is augmented in HDM-induced AR patients who experienced SRs during SCIT. Despite this, SCIT remains effective in these patients when administered with low-dosage allergen extracts., (© 2024 The Author(s). Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Sublingual allergen immunotherapy (SLIT) is an emerging treatment option for allergic asthma and a potential disease-modifying strategy for asthma prevention. The key cellular events leading to such long-term tolerance remain to be fully elucidated. We administered prophylactic SLIT in a mouse model of house dust mite (HDM)-driven allergic asthma. HDM extract was sublingually administered over 3 weeks followed by intratracheal sensitization and intranasal challenges with HDM. Prophylactic SLIT prevented allergic airway inflammation and hyperreactivity with a low lab-to-lab variation. The HDM-specific T helper (Th)2 (cluster of differentiation 4 Th) response was shifted by SLIT toward a regulatory and Th17 response in the lung and mediastinal lymph node. By using Derp1-specific cluster of differentiation 4 + T cells (1-DER), we found that SLIT blocked 1-DER T cell recruitment to the mediastinal lymph node and dampened IL-4 secretion following intratracheal HDM sensitization. Sublingually administered Derp1 protein activated 1-DER T cells in the cervical lymph node via chemokine receptor7 + migratory dendritic cells (DC). DCs migrating from the oral submucosa to the cervical lymph node after SLIT-induced Foxp3 + regulatory T cells. When mice were sensitized with HDM, prior prophylactic SLIT increased Derp1 specific regulatory T cells (Tregs) and lowered Th2 recruitment in the lung. By using Foxp3-diphtheria toxin receptor mice, Tregs were found to contribute to the immunoregulatory prophylactic effect of SLIT on type 2 immunity. These findings in a mouse model suggest that DC-mediated functional Treg induction in oral mucosa draining lymph nodes is one of the driving mechanisms behind the disease-modifying effect of prophylactic SLIT., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Neutrophilic asthma is generally defined by poorly controlled symptoms and high levels of neutrophils in the lungs. Short-chain fatty acids (SCFAs) are proposed as nonpharmacological therapy for allergic asthma, but their impact on the neutrophilic asthma lacks evidence. SCFAs regulate immune cell responses and impact the inflammasome NLRP3, a potential pharmacological target for neutrophilic asthma. Here, we explored the capacity of SCFAs to mitigate murine-induced neutrophilic asthma and the contribution of NLRP3 to this asthma. The objective of this study is to analyze whether SCFAs can attenuate lung inflammation and tissue remodeling in murine neutrophilic asthma and NLRP3 contribution to this endotype. Wild-type (WT) C57BL6 mice orotracheally received 10 μg of HDM (house dust mite) in 80 μL of saline on days 0, 6-10. To explore SCFAs, each HDM group received 200 mM acetate, propionate, or butyrate. To explore NLRP3, Nlrp3 KO mice received the same protocol of HDM. On the 14th day, after euthanasia, bronchoalveolar lavage fluid (BALF) and lungs were collected to evaluate cellularity, inflammatory cytokines, and tissue remodeling. HDM group had increased BALF neutrophil influx, TNF-α, IFN-γ, IL-17A, collagen deposition, and mucus secretion compared to control. SCFAs distinctively attenuate lung inflammation. Only features of tissue remodeling were Nlrp3-dependent such as collagen deposition, mucus secretion, active TGF-β cytokine, and IMs CD206 + . SCFAs greatly decreased inflammatory cytokines and tissue remodeling. Only tissue remodeling was dependent on NLRP3. It reveals the potential of SCFAs to act as an additional therapy to mitigate neutrophilic asthma and the NLRP3 contribution to asthma., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Human IgE (hIgE) mAbs against major mite allergen Der p 2 developed using human hybridoma technology were used for IgE epitope mapping and analysis of epitopes associated with the hIgE repertoire., Objective: We sought to elucidate the new hIgE mAb 4C8 epitope on Der p 2 and compare it to the hIgE mAb 2F10 epitope in the context of the allergenic structure of Der p 2., Methods: X-ray crystallography was used to determine the epitope of anti-Der p 2 hIgE mAb 4C8. Epitope mutants created by targeted mutagenesis were analyzed by immunoassays and in vivo using a human high-affinity IgE receptor (FcεRIα)-transgenic mouse model of passive systemic anaphylaxis., Results: The structure of recombinant Der p 2 with hIgE mAb 4C8 Fab was determined at 3.05 Å. The newly identified epitope region does not overlap with the hIgE mAb 2F10 epitope or the region recognized by 3 overlapping hIgE mAbs (1B8, 5D10, and 2G1). Compared with wild-type Der p 2, single or double 4C8 and 2F10 epitope mutants bound less IgE antibodies from allergic patients by as much as 93%. Human FcεRIα-transgenic mice sensitized by hIgE mAbs, which were susceptible to anaphylaxis when challenged with wild-type Der p 2, could no longer cross-link FcεRI to induce anaphylaxis when challenged with the epitope mutants., Conclusions: These data establish the structural basis of allergenicity of 2 hIgE mAb nonoverlapping epitopes on Der p 2, which appear to make important contributions to the hIgE repertoire against Der p 2 and provide molecular targets for future design of allergy therapeutics., Competing Interests: Disclosure statement Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) (award nos. R01AI077653-13 [to A.P., M.D.C., and M.C.] and R01AI155668 and R21AI123307 [to S.A.S.]). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The research was supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES102906 [to G.A.M.]). The structural results shown in this report are derived from data collected at Southeast Regional Collaborative Access Team (SER-CAT; 22ID) beamline at the Advanced Photon Source, Argonne National Laboratory. Supporting institutions may be found at www.ser-cat.org/members.html. Use of the Advanced Photon Source was supported by the US Department of Energy, Office of Science, Office of Basic Energy Sciences (contract nos. DE-AC02-06CH11357 and W-31-109-Eng-38). This work was partially supported by an ASPIRE III grant from the Office of the Vice President of Research at the University of South Carolina. This research is funded by the above mentioned NIH/NIAID award to InBio. Disclosure of potential conflict of interest: A. Pomés is an employee of InBio; and is the contact principal investigator of the NIH R01 award that provided funding for the study. M.D. Chapman is an employee of InBio; has a financial interest in InBio; and is a co-investigator on the NIH R01 award. A. Ball is an employee of InBio. The hIgE mAbs and some of the allergens described herein were produced by InBio. InBio has a license agreement with the VUMC for commercialization of hIgE mAbs for research and diagnostic purposes. The hIgE mAbs covered by this agreement are available from InBio (www.inbio.com). S.A. Smith is an inventor on US patent 10908168-B2 for generation of hIgE mAbs; has received patent royalties; and has related patents pending. The rest of the authors declare that they have no relevant conflicts of interest., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Allergic asthma is a complex inflammatory disorder predominantly orchestrated by T helper 2 (Th2) lymphocytes. The anti-inflammatory protein Clara Cell 10-kDa (CC10), also known as secretoglobin family 1A member 1 (SCGB1A1), shows promise in modulating respiratory diseases. However, its precise role in asthma remains unclear. This study examines the potential of CC10 to suppress allergic asthma inflammation, specifically assessing its regulatory effects on Th2 cell responses and dendritic cells (DCs). Lower CC10 levels in asthma were observed and correlated with increased IgE and lymphocytes. Cc10 -/- mice exhibited exacerbated allergic airway inflammation marked by increased inflammatory cell infiltration, Th2 cytokines, serum antigen-specific IgE levels, and airway hyperresponsiveness (AHR) in house dust mite (HDM)-induced models. Conversely, recombinant CC10 significantly attenuated these inflammatory responses. Intriguingly, CC10 did not directly inhibit Th cell activation but significantly downregulated the population of CD11b + CD103 - DCs subsets in lungs of asthmatic mice and modulated the immune activation functions of DCs through NF-κB signaling pathway. The mixed lymphocyte response assay revealed that DCs mediated the suppressive effect of CC10 on Th2 cell responses. Collectively, CC10 profoundly mitigates Th2-type allergic inflammation in asthma by modulating lung DC phenotype and functions, highlighting its therapeutic potential for inflammatory airway conditions and other related immunological disorders., (© 2024. The Author(s).)

Objective: The study aims to preliminarily investigate the prevalence characteristics of allergen-specific immunoglobulin E (IgE) in 57558 patients over the past decade by examining its distribution in the province and exploring its associations with age, sex, temperature, and relative humidity, providing insights for the prevention and diagnosis of allergic diseases in the Sichuan region., Methods: A retrospective analysis was conducted on a cohort of 57558 patients who underwent allergen testing (by means of EUROIMMUN immunoblotting method) at West China Hospital, Sichuan University between August 2012 and February 2022. The clinical data of these patients were collected to establish a comprehensive database, while the temperature and humidity records of the corresponding timeframe were gathered for further analysis. The positive results from the allergen tests were categorized into four levels, including weakly positive (±), positive (+), moderately positive (++), and strongly positive (+++). Statistical analyses were performed using SPSS 25.0, with Chi-square tests conducted to compare count data and Pearson's correlation tests done conducted to assess the relationships between different types of allergens and temperature/relative humidity. P <0.05 was applied to determine statistically significant differences. GraphPad Prism 9.0.0 was utilized to generate visual representations of the data., Results: The overall positivity rate of allergen-specific IgE among the 57558 samples was 30.69%. The top five allergens that elicited positive results were dust mite mix 1 (14.46%), crab (6.67%), soybean (4.72%), fish mix 1 (4.64%), and cockroach (4.34%). Notably, weakly positive (±) results were predominant for allergens such as eggs, peanuts, soybeans, cow's milk, beef, mutton, crab, shrimp, fish mix 1, cockroach, humulus japonicus , ambrosia artemisifolia , artemisia vulgaris , tree mix 2, house dust, and mold mix 1, collectively constituting over 40% of the positive outcomes. In contrast, cat hair and dog dander exhibited an equal distribution of approximately 25% for each positive levels, while mite mix 1 demonstrated the highest proportion of strongly positive results (+++), accounting for 37.66% of all positive results. Sex disparities in positivity rates were evident for various allergens, with significant differences observed for peanut, soybean, crab, shrimp, fish mix 1, cockroach, ambrosia artemisifolia , tree mix 2, cat hair, dog dander, and mite mix 1. Furthermore, the study identified age-related trends in allergen positivity rates, with a general decline observed across most allergens with increasing age. The positive rate of at least one food allergen was highest in the 0-10 age group (36.18%), and the positive rate of at least one inhalation allergen was highest in the 11-20 age group (45.35%). Noteworthy correlations were observed between allergen-specific IgE positivity and environmental factors, including a strong negative correlation between cow's milk allergy and relative humidity ( r =-0.640, P <0.05), a strong negative correlation of artemisia vulgaris sensitivity with temperature ( r Mean high temperature =-0.695, r Mean low temperature =-0.692, P <0.05), and a very strong positive correlation of mold mix 1 sensitivity with relative humidity ( r =0.704, P <0.05)., Conclusion: Allergen-specific IgE positivity is associated with genetic factors, demonstrates significant sex- and age-related characteristics in the population, and is influenced by changes in local temperature and relative humidity., Competing Interests: 利益冲突　所有作者均声明不存在利益冲突, (© 2024《四川大学学报（医学版）》编辑部 版权所有Copyright ©2024 Editorial Office of Journal of Sichuan University (Medical Sciences).)

Atopic dermatitis (AD) is a chronic and recurrent inflammatory disease caused by abnormalities in skin immunoregulation. House dust mite can directly damage the skin barrier and thus sensitize the skin, which is one of the main allergens inducing AD in humans and widely exists in daily life. Meanwhile, the accompanying bacterial infections and exposure to additional allergens exacerbate the condition by generating excessive reactive oxygen species (ROS). Herein, we have developed the CPDP hydrogel with injectable and self-healing ability to combat pathogenic microorganisms and inflammatory environments for AD therapy. In vitro experiments have affirmed the efficacy of the CPDP hydrogel in combating mites, killing bacteria, and scavenging ROS. In a mouse model closely mimicking HDM-induced AD, the CPDP hydrogel has shown superior therapeutic effects, including reducing epidermal thickness and mast cell count, increasing collagen deposition, as well as down-regulating pro-inflammatory factors.