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Summary: N6-methyladenosine (m6A) modification has been implicated in many cell processes and diseases. YTHDF1, a translation-facilitating m6A reader, has not been previously shown to be related to allergic airway inflammation. Here, we report that YTHDF1 is highly expressed in allergic airway epithelial cells and asthmatic patients and that it influences proinflammatory responses. CLOCK, a subunit of the circadian clock pathway, is the direct target of YTHDF1. YTHDF1 augments CLOCK translation in an m6A-dependent manner. Allergens enhance the liquid-liquid phase separation (LLPS) of YTHDF1 and drive the formation of a complex comprising dimeric YTHDF1 and CLOCK mRNA, which is distributed to stress granules. Moreover, YTHDF1 strongly activates NLRP3 inflammasome production and interleukin-1β secretion leading to airway inflammatory responses, but these phenotypes are abolished by deleting CLOCK. These findings demonstrate that YTHDF1 is an important regulator of asthmatic airway inflammation, suggesting a potential therapeutic target for allergic airway inflammation.

Abstract CRISPR-Cas systems are an immune defense mechanism that is widespread in archaea and bacteria against invasive phages or foreign genetic elements. In the last decade, CRISPR-Cas systems have been a leading gene-editing tool for agriculture (plant engineering), biotechnology, and human health (e.g., diagnosis and treatment of cancers and genetic diseases), benefitted from unprecedented discoveries of basic bacterial research. However, the functional complexity of CRISPR systems is far beyond the original scope of immune defense. CRISPR-Cas systems are implicated in influencing the expression of physiology and virulence genes and subsequently altering the formation of bacterial biofilm, drug resistance, invasive potency as well as bacterial own physiological characteristics. Moreover, increasing evidence supports that bacterial CRISPR-Cas systems might intriguingly influence mammalian immune responses through targeting endogenous genes, especially those relating to virulence; however, unfortunately, their underlying mechanisms are largely unclear. Nevertheless, the interaction between bacterial CRISPR-Cas systems and eukaryotic cells is complex with numerous mysteries that necessitate further investigation efforts. Here, we summarize the non-canonical functions of CRISPR-Cas that potentially impact bacterial physiology, pathogenicity, antimicrobial resistance, and thereby altering the courses of mammalian immune responses.

Abstract Little is known about the epidemiology and impact of atrial fibrillation (AF) on cardiovascular diseases (CVD) mortality among hypertensive elderly population in northeast China. The community‐based study included 4497 hypertensive elderly residents aged ≥65 years who lived in northeast China from September 2017 to March 2019. Information on CVD deaths was obtained from baseline until July 31, 2021. Cox proportional hazard regression models were performed in the evaluation of CVD mortality. We identified 101 persons with AF. The prevalence of AF was 2.2% among elderly hypertensive population, which increased significantly with age. The prevalence of AF was higher in men than in women. The awareness rate was 51.5%, higher in urban areas than in rural areas (68.8% vs 43.5%, P = .018). Only 4.0% patients received oral anticoagulant (OAC) therapy among AF patients. Moreover, diabetes (26.7%) and dyslipidemia (37.6%) were highly prevalent in AF patients. Furthermore, 212 persons died due to CVD (14.7/1000 person‐years) during a median follow‐up of 3.2 years. AF patients had a 3.42 (95% CI: 2.07‐5.63) times higher risk of CVD mortality than the patients without AF in the fully adjusted model. Therefore, the burden of AF among hypertensive elderly population in northeast China was considerable. Long‐term screening and management strategies for AF and related risk factors are required among hypertensive elderly in northeast China.

ABSTRACT The therapeutic use of bacteriophages (phages) provides great promise for treating multidrug-resistant (MDR) bacterial infections. However, an incomplete understanding of the interactions between phages and bacteria has negatively impacted the application of phage therapy. Here, we explored engineered anti-CRISPR (Acr) gene-containing phages (EATPs, eat Pseudomonas) by introducing Type I anti-CRISPR (AcrIF1, AcrIF2, and AcrIF3) genes into the P. aeruginosa bacteriophage DMS3/DMS3m to render the potential for blocking P. aeruginosa replication and infection. In order to achieve effective antibacterial activities along with high safety against clinically isolated MDR P. aeruginosa through an anti-CRISPR immunity mechanism in vitro and in vivo, the inhibitory concentration for EATPs was 1 × 108 PFU/mL with a multiplicity of infection value of 0.2. In addition, the EATPs significantly suppressed the antibiotic resistance caused by a highly antibiotic-resistant PA14 infection. Collectively, these findings provide evidence that engineered phages may be an alternative, viable approach by which to treat patients with an intractable bacterial infection, especially an infection by clinically MDR bacteria that are unresponsive to conventional antibiotic therapy. IMPORTANCE Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic Gram-negative bacterium that causes severe infection in immune-weakened individuals, especially patients with cystic fibrosis, burn wounds, cancer, or chronic obstructive pulmonary disease (COPD). Treating P. aeruginosa infection with conventional antibiotics is difficult due to its intrinsic multidrug resistance. Engineered bacteriophage therapeutics, acting as highly viable alternative treatments of multidrug-resistant (MDR) bacterial infections, have great potential to break through the evolutionary constraints of bacteriophages to create next-generation antimicrobials. Here, we found that engineered anti-CRISPR (Acr) gene-containing phages (EATPs, eat Pseudomonas) display effective antibacterial activities along with high safety against clinically isolated MDR P. aeruginosa through an anti-CRISPR immunity mechanism in vitro and in vivo. EATPs also significantly suppressed the antibiotic resistance caused by a highly antibiotic-resistant PA14 infection, which may provide novel insight toward developing bacteriophages to treat patients with intractable bacterial infections, especially infections by clinically MDR bacteria that are unresponsive to conventional antibiotic therapy.

Abstract Bitter receptors function primarily in sensing taste, but may also have other functions, such as detecting pathogenic organisms due to their agile response to foreign objects. The mouse taste receptor type-2 member 138 (TAS2R138) is a member of the G-protein-coupled bitter receptor family, which is not only found in the tongue and nasal cavity, but also widely distributed in other organs, such as the respiratory tract, gut, and lungs. Despite its diverse functions, the role of TAS2R138 in host defense against bacterial infection is largely unknown. Here, we show that TAS2R138 facilitates the degradation of lipid droplets (LDs) in neutrophils during Pseudomonas aeruginosa infection through competitive binding with PPARG (peroxisome proliferator-activated receptor gamma) antagonist: N-(3-oxododecanoyl)-l-homoserine lactone (AHL-12), which coincidently is a virulence-bound signal produced by this bacterium (P. aeruginosa). The released PPARG then migrates from nuclei to the cytoplasm to accelerate the degradation of LDs by binding PLIN2 (perilipin-2). Subsequently, the TAS2R138–AHL-12 complex targets LDs to augment their degradation, and thereby facilitating the clearance of AHL-12 in neutrophils to maintain homeostasis in the local environment. These findings reveal a crucial role for TAS2R138 in neutrophil-mediated host immunity against P. aeruginosa infection.

BackgroundEosinophils act as a secondary antigen-presenting cell (APC) to stimulate Th cell responses against antigens. IL-25 plays a significant role in eosinophil activation in allergic asthma. The role of IL-25 on the classic APC functions of dendritic cells has been elucidated. However, whether IL-25 facilitates eosinophils for antigen presentation is unknown.ObjectiveTo elucidate the role of IL-25 on eosinophils antigen presenting function during allergic asthma and its related mechanism.MethodsEosinophils from allergic asthma subjects were cultured with IL-25 and HDM to identify the co-stimulator molecules expression. Co-cultures of patient eosinophils and autologous naïve CD4+ T cells in the same culture system were to explore whether eosinophils had the capacity to promote Th cell differentiation in response to IL-25 engagement. In asthma mouse model, IL-25-/- mice were exposed to HDM to investigate the effect of IL-25 on eosinophils during the sensitization phase. The impact of IL-25 on the capacity for eosinophils taking up antigens was evaluated. Mouse bone marrow derived eosinophils (BmEOS) were co-cultured with naïve CD4+T cells sorted from spleens under HDM and IL-25 stimulation to identify T cell differentiation.ResultsIL-25 upregulated HLA-DR, PD-L1, and OX-40L expression on eosinophils from allergic asthma patients. IL-25 and HDM co-sensitized eosinophils promoted Th2 differentiation. In mouse model, IL-25-/- mice experienced restrained allergic pulmonary inflammation and reduced eosinophils recruitment and antigen uptake capacity during the early sensitization phase. In vitro, IL-25 promoted antigen uptake by eosinophils. In BmEOS and naïve CD4+T cells co-culture, IL-25 accreted the proportion of CD4+Th2 cells, which was absent in CD4+T cells culture alone.ConclusionOur data identify a novel role of IL-25 in enhancing eosinophils antigen uptake and co-stimulator molecules expression to induce Th2 priming in the context of allergic inflammation.

BackgroundElderly people are susceptible to atrial fibrillation (AF) and ischemic stroke (IS); however, less information is known about the association between AF and the risk of cardiovascular disease (CVD) mortality in elderly population with IS. We aimed to investigate the features of AF among aged people with IS and to illustrate whether AF accounted for CVD mortality.MethodsAt baseline, 790 patients with IS were enrolled from the general northeast Chinese elderly population (>60 years) between September 2017 to March 2019. The prevalence, awareness, and treatment of AF in each age group were analyzed, as well as major-related cardiovascular risk factors. The population was followed until July 31, 2021, and information on CVD death was obtained.ResultsA total of 25 people had AF, and the prevalence of AF in the elderly population with IS was 3.2%. The AF prevalence grew along with age from 1% (60–64 years) to 4.3% (70–74 years) and 4.2% (≥75 years), which was higher in the urban residents than in the rural residents (5.7 vs. 2.2%, P = 0.014). The awareness and treatment rates of patients with AF were 80 and 8%. After a median follow-up period of 3.3 years, 58 subjects died due to CVD and 5 subjects were accompanied with AF (rate 70.6/1,000 person-years). Elderly IS patients with AF had a 3.65-fold increased risk of CVD death in the fully adjusted model when compared with non-AF participants.ConclusionThe AF prevalence increased with age among the elderly population with IS. Moreover, elderly patients with IS in northeast China with AF had a higher CVD mortality. Therefore, early screening and prompt management of AF in elderly population with IS in northeast China are required.

Heme oxygenase-1 (HO-1) is not only a rate-limiting enzyme in heme metabolism but is also regarded as a protective protein with an immunoregulation role in asthmatic airway inflammation. HO-1 exerts an anti-inflammation role in different stages of airway inflammation via regulating various immune cells, such as dendritic cells, mast cells, basophils, T cells, and macrophages. In addition, the immunoregulation role of HO-1 may differ according to subcellular locations.

SHIP-1 is an inositol phosphatase that hydrolyzes phosphatidylinositol 3-kinase (PI3K) products and negatively regulates protein kinase B (Akt) activity, thereby modulating a variety of cellular processes in mammals. However, the role of SHIP-1 in bacterial-induced sepsis is largely unknown. Here, we show that SHIP-1 regulates inflammatory responses during Gram-negative bacterium Pseudomonas aeruginosa infection. We found that infected-SHIP-1−/− mice exhibited decreased survival rates, increased inflammatory responses, and susceptibility owing to elevated expression of PI3K than wild-type (WT) mice. Inhibiting SHIP-1 via siRNA silencing resulted in lipid raft aggregates, aggravated oxidative damage, and bacterial burden in macrophages after PAO1 infection. Mechanistically, SHIP-1 deficiency augmented phosphorylation of PI3K and nuclear transcription of signal transducer and activator of transcription 5 (STAT5) to induce the expression of Trib1, which is critical for differentiation of M2 but not M1 macrophages. These findings reveal a previously unrecognized role of SHIP-1 in inflammatory responses and macrophage homeostasis during P. aeruginosa infection through a PI3K/Akt–STAT5–Trib1 axis.

Invariant natural killer T (iNKT) cells play important roles in bridging innate and adaptive immunity via rapidly producing a variety of cytokines. A small subset of iNKT cells produces IL-17 and is generated in the thymus during iNKT-cell ontogeny. The mechanisms that control the development of these IL-17-producing iNKT-17 cells (iNKT-17) are still not well defined. Diacylglycerol kinase ζ (DGKζ) belongs to a family of enzymes that catalyze the phosphorylation and conversion of diacylglycerol to phosphatidic acid, two important second messengers involved in signaling from numerous receptors. We report here that DGKζ plays an important role in iNKT-17 development. A deficiency of DGKζ in mice causes a significant reduction of iNKT-17 cells, which is correlated with decreased RORγt and IL-23 receptor expression. Interestingly, iNKT-17 defects caused by DGKζ deficiency can be corrected in chimeric mice reconstituted with mixed wild-type and DGKζ-deficient bone marrow cells. Taken together, our data identify DGKζ as an important regulator of iNKT-17 development through iNKT-cell extrinsic mechanisms.

Abstract Background Human blood metabolites have demonstrated close associations with chronic kidney disease (CKD) in observational studies. Nonetheless, the causal relationship between metabolites and CKD is still unclear. This study aimed to assess the associations between metabolites and CKD risk. Methods We applied a two-sample Mendelian randomization (MR) analysis to evaluate relationships between 1400 blood metabolites and eight phenotypes (outcomes) (CKD, estimated glomerular filtration rate(eGFR), urine albumin to creatinine ratio, rapid progress to CKD, rapid decline of eGFR, membranous nephropathy, immunoglobulin A nephropathy, and diabetic nephropathy). The inverse variance weighted (IVW), MR-Egger, and weighted median were used to investigate the causal relationship. Sensitivity analyses were performed with Cochran’s Q, MR-Egger intercept, MR-PRESSO Global test, and leave-one-out analysis. Bonferroni correction was used to test the strength of the causal relationship. Results Through the MR analysis of 1400 metabolites and eight clinical phenotypes, a total of 48 metabolites were found to be associated with various outcomes. Among them, N-acetylleucine (OR = 0.923, 95%CI: 0.89–0.957, P IVW = 1.450 × 10–5) has a strong causal relationship with lower risk of CKD after the Bonferroni-corrected test, whereas Glycine to alanine ratio has a strong causal relationship with higher risk of CKD (OR = 1.106, 95%CI: 1.063–1.151, P IVW = 5.850 × 10–7). No horizontal pleiotropy and heterogeneity were detected. Conclusion Our study offers groundbreaking insights into the integration of metabolomics and genomics to reveal the pathogenesis of and therapeutic strategies for CKD. It underscores 48 metabolites as potential causal candidates, meriting further investigation.

BackgroundObservational studies have suggested an association between obstructive sleep apnea (OSA), chronic kidney disease (CKD), and renal function, and vice versa. However, the results from these studies are inconsistent. It remains unclear whether there are causal relationships and in which direction they might exist.MethodsWe used a two-sample Mendelian randomization (MR) method to investigate the bidirectional causal relation between OSA and 7 renal function phenotypes [creatinine-based estimated glomerular filtration rate (eGFRcrea), cystatin C-based estimated glomerular filtration rate (eGFRcys), blood urea nitrogen (BUN), rapid progress to CKD, rapid decline of eGFR, urinary albumin to creatinine ratio (UACR) and CKD]. The genome-wide association study (GWAS) summary statistics of OSA were retrieved from FinnGen Consortium. The CKDGen consortium and UK Biobank provided GWAS summary data for renal function phenotypes. Participants in the GWAS were predominantly of European ancestry. Five MR methods, including inverse variance weighted (IVW), MR-Egger, simple mode, weighted median, and weighted mode were used to investigate the causal relationship. The IVW result was considered the primary outcome. Then, Cochran’s Q test and MR-Egger were used to detect heterogeneity and pleiotropy. The leave-one-out analysis was used for testing the stability of MR results. RadialMR was used to identify outliers. Bonferroni correction was applied to test the strength of the causal relationships (p

PurposeObservational studies have reported inconsistent results on the relationship between chronic kidney disease (CKD) and age-related macular degeneration (AMD). The primary objective of this study was to investigate the causal relationships between estimated glomerular filtration rate (eGFR), CKD, its common causes, and AMD among participants of European descent.MethodsGenetic variants associated with eGFR, CKD and its common causes, encompassing diabetic nephropathy (DN), immunoglobulin A nephropathy (IgAN), and membranous nephropathy (MN) were obtained from previously published genome-wide association studies (GWAS) and FinnGen database. Summary statistics for early AMD, AMD, dry AMD, and wet AMD were acquired from the GWAS and FinnGen database. Inverse-variance-weighted (IVW) method was the main MR analysis. Sensitivity analyses were performed with Cochran’s Q, MR-Egger intercept, and leave-one-out analysis. In addition, RadialMR was utilized to identify and remove outliers.ResultsIVW results showed that CKD, eGFR were not associated with any type of AMD (p > 0.05). DN (OR: 1.042, 95% CI: 1.002–1.083, p = 0.037) and MN (OR: 1.023, 95% CI: 1.007–1.040, p = 0.005) were associated with an increased risk of earl AMD. DN (OR: 1.111, 95% CI: 1.07–1.154, p = 4.87 × 10−8), IgAN (OR: 1.373, 95% CI: 1.097–1.719, p = 0.006), and MN (OR: 1.036, 95% CI: 1.008–1.064, p = 0.012) were associated with an increased risk of AMD. DN (OR: 1.090, 95% CI: 1.042–1.140, p = 1.57 × 10−4) and IgAN (OR: 1.480, 95% CI: 1.178–1.858, p = 7.55 × 10−4) were associated with an increased risk of dry AMD. The risk of wet AMD was associated with DN (OR: 1.107, 95% CI: 1.043–1.174, p = 7.56 × 10−4) and MN (OR: 1.071, 95% CI: 1.040–1.103, p = 5.48 × 10−6).ConclusionThis MR study found no evidence of causal relationship between CKD and AMD. DN, IgAN, and MN may increase risk of AMD. This findings underscore the importance of ocular examinations in patients with DN, MN, and IgAN. More studies are needed to support the findings of our current study.

A high-quality ZnTe and TeO2 (ZTO) composite is grown on an n-type silicon substrate, using a modified metal-assisted chemical vapor deposition method. Self-powered photodetector based on a ZnTe–TeO2 composite/Si heterojunction with ultra-broadband and high responsivity is obtained. The photosensitive detection performances of the ZTO composite/Si heterojunction photodetector are assessed using photoresponse spectrum. The photodetector shows ultra-broadband photoresponsivity from UV to NIR lights as ZnTe has a moderate, direct band gap of 2.26 eV, TeO2 has a wide band gap of 4.0 eV, and Si has a narrow band gap of 1.12 eV. Upon exposure to 850 nm light at a zero-bias voltage, the detector shows a high responsivity of 75 mA/W, detectivity of 1.4 × 1013 cm Hz1/2/W, fast response and recovery properties with response and recovery times both below 0.61 s, respectively. The working mechanism is illustrated from the band energy diagram of ZnTe/Si heterojunction and the high transmittance of TeO2. [ABSTRACT FROM AUTHOR]

The nonlinear dynamics of incompressible non-dissipative two-fluid plasma model is investigated through classical Gibbs ensemble methods. Liouville's theorem of phase space for each wave number is proved, and the absolute equilibrium spectra for Galerkin truncated two-fluid model are calculated. In two-fluid theory, the equilibrium is built on the conservation of three quadratic invariants: the total energy and the self-helicities for ions and electrons fluid, respectively. The implications of statistic equilibrium spectra with arbitrary ratios of conserved invariants are discussed. [ABSTRACT FROM AUTHOR]

By using analytical method, the exact solutions of the incompressible dissipative Hall magnetohydrodynamics (MHD) equations are derived. It is found that a phase difference may occur between the velocity and magnetic field fluctuations when the kinetic and magnetic Reynolds numbers are both very large. Since velocity and magnetic field fluctuations are both circular polarized, the phase difference makes them no longer parallel or anti-parallel like that in the incompressible ideal Hall MHD. [ABSTRACT FROM AUTHOR]

Background: Airway inflammation is mainly mediated by T helper 2 cells (Th2) that characteristically produce interleukin (IL)-4, IL-5, and IL-13. Epidemiological studies have revealed an inverse association between the dietary intake of vitamin A and the occurrence of asthma. Serum vitamin A concentrations are significantly lower in asthmatic subjects than in healthy control subjects. It has been reported that all-trans retinoic acid (ATRA), a potent derivative of vitamin A, regulates immune responses. However, its role in Th2-mediated airway inflammation remains unclear. We investigated the effects of ATRA in a mouse model of allergic airway inflammation. Results: We found that ATRA treatment attenuated airway inflammation and decreased mRNA levels of Th2- and Th17-related transcription factors. The data showed that airway inflammation coincided with levels of Th2- and Th17-related cytokines. We also showed that ATRA inhibited Th17 and promoted inducible regulatory T-cell differentiation, whereas it did not induce an obvious effect on Th2 differentiation in vitro. Our data suggest that ATRA may interfere with the in vivo Th2 responses via T-cell extrinsic mechanisms. Conclusions: Administration of ATRA dramatically attenuated airway inflammation by inhibiting Th2 and Th17 differentiation and/or functions. ATRA may have potential therapeutic effects for airway inflammation in asthmatic patients. [ABSTRACT FROM AUTHOR]

Background: Antigen-specific immunotherapy (SIT) has been widely practiced in treating allergic diseases such as asthma. However, this therapy may induce a series of allergic adverse events during treatment. Peptide immunotherapy (PIT) was explored to overcome these disadvantages. We confirmed that multiple antigen peptides (MAPs) do not cause autoimmune responses, which led to the presumption that MAPs intervention could alleviate allergic airway inflammation without inducing adverse effects. Results: In this study, synthesized OVA323-339MAP octamers were subcutaneously injected into ovalbumin (OVA)-sensitized and -challenged Balb/c mice to observe its effect on allergic airway inflammation, Th2 immune response, and immune regulating function. It was confirmed that OVA sensitization and challenge led to significant peritracheal inflammatory, cell infiltration, and intensive Th2 response. Treatment of OVA323-339MAP octomers in theairway inflammation mice model increased CD4+CD25+Foxp3+ T regulatory (Treg) cells and their regulatory function in peripheral blood, mediastinal draining lymph nodes, and the spleen. Furthermore, OVA323-339MAP increased IL-10 levels in bronchial alveolar lavage fluid (BALF); up-regulated the expression of IL-10, membrane-bound TGF-β1, as well as Foxp3 in lung tissues; and up-regulated programmed death-1 (PD-1) and cytotoxic T lymphocyte associated antigen 4 (CTLA-4) on the surface of Treg cells. These results were further correlated with the decreased OVA specific immunoglobulin E (sIgE) level and the infiltration of inflammatory cells such as eosinophils and lymphocytes in BALF. However, OVA323-339 peptide monomers did not show any of the mentioned effects in the same animal model. Conclusions: Our study indicates that OVA323-339MAP had significant therapeutic effects on mice allergic airway inflammation by regulating the balance of Th1/Th2 response through Treg cells in vivo. [ABSTRACT FROM AUTHOR]

As one of the active structural health monitoring methods based on the Lamb wave, the ultrasonic phased-array damage detection method can provide information such as damage location and range more intuitively, which is why this method is a research hotspot in the field of Lamb wave-based damage monitoring. However, the ultrasonic phased-array damage detection method intended for the far field is not applicable to near-field damage monitoring. In addition, the traditional one-dimensional piezoelectric phased-array damage imaging method suffers from a blind area in the near field, and the data collection time of its angle scanning is relatively long. In view of these problems, this paper proposes an omnidirectional damage imaging monitoring method, combining the near-field sampling phased-array damage monitoring algorithm and the two-dimensional phased-array. The proposed method is verified by experiments using complex composite materials, and the results obtained show that the proposed omnidirectional near-field sampling phased-array damage imaging method is suitable for real-time damage detection in complex composite materials.

Asthma is characterized by increased airway submucosal infiltration of T helper (Th) cells and myeloid cells that co-conspire to sustain a chronic inflammation. While recent studies have demonstrated that the myeloid basophils promote Th2 cells in response to various types of allergens, the underlying mechanisms are poorly understood. Here, we found for the first time that in a mouse model of allergic asthma basophils highly expressed OX40 ligand (OX40L) after activation. Interestingly, blockade of OX40-OX40L interaction suppressed basophilsprimed Th2 cell differentiation in vitro and ameliorated ovalbumin (OVA)-induced allergic eosinophilic inflammation mediated by Th2 activation. In accordance, the adoptive transfer of basophils derived from mediastinal lymph nodes (MLN) of OVA-immunized mice triggered a robust Th2 response and eosinophilic inflammation in wild-type mice but largely muted in OX40-/- mice and mice receiving OX40L-blocked basophils. Taken together, our results reveal a critical role of OX40L presented by the activated basophils to initiate Th2 responses in an allergic asthma model, implicating OX40-OX40L signaling as a potential therapeutic target in the treatment of allergic airway inflammation. [ABSTRACT FROM AUTHOR]

Allergic asthma is conventionally considered as a Th2 immune response characterized by eosinophilic inflammation. Recent investigations revealed that Th17 cells play an important role in the pathogenesis of non-eosinophilic asthma (NEA), resulting in steroid-resistant neutrophilic airway inflammation. Heme oxygenase-1 (HO-1) has anti-inflammation, anti-oxidation, and anti-apoptosis functions. However, its role in NEA is still unclear. Here, we explore the role of HO-1 in a mouse model of NEA. HO-1 inducer hemin or HO-1 inhibitor tin protopor-phyrin IX was injected intraperitoneally into ovalbumin-chal-lenged DO1 1.10 mice. Small interfering RNA (siRNA) was delivered into mice to knock down HO-1 expression. The results show that induction of HO-1 by hemin attenuated airway inflammation and decreased neutrophil infiltration in bronchial alveolar lavage fluid and was accompanied by a lower proportion of Th17 cells in mediastinal lymph nodes and spleen. More importantly, induction of HO-1 down-regulated Th17-related transcription factor retinoic acid-related orphan receptor yt (RORyt) expression and decreased IL-17A levels, all of which correlated with a decrease in phosphorylated STAT3 (p-STAT3) level and inhibition of Th17 cell differentiation. Consistently, the above events could be reversed by tin protoporphyrin IX. Also, HO-1 siRNA transfection abolished the effect of hemin induced HO-1 in vivo. Meanwhile, the hemin treatment promoted the level of Foxp3 expression and enhanced the proportion of regulatory T cells (Tregs). Collectively, our findings indicate that HO-1 exhibits anti-inflammatory activity in the mouse model of NEA via inhibition of the p-STAT3-RORγt pathway, regulating kinetics of RORγt and Foxp3 expression, thus providing a possible novel therapeutic target in asthmatic patients. [ABSTRACT FROM AUTHOR]

The article presents the expression of concern issued by the editorial board on a report that a research technician in the animal pulmonary physiology laboratory fabricated and/or falsified data in the article "iNKT Cells Require TSC1 for Terminal Maturation and Effector Lineage Fate Decisions."