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Background: Uncontrolled severe eosinophilic chronic rhinosinusitis (eCRS) is associated with elevated levels of Th2 cells and raised immunoglobulin concentrations in nasal polyp tissue. eCRS is characterized by high eosinophilic infiltration and type 2 inflammation. Gαi1/3 proteins participate in allergic inflammation by regulating immune cells. Whether Gαi1/3 proteins have a role in the development of eCRS remains unknown. Objectives: To investigate the association between Gαi1/3 expression levels and CRS and the underlying mechanisms Methods: Western blotting and immunohistology were used to detect Gαi1/3 expression. Correlations between Gαi1/3 and immune cells and clinical parameters were analyzed. Signaling pathway activation in IL-5-induced Gαi1/3-knockout or knockdown mouse embryonic fibroblasts (MEFs) and eosinophils (EoL-1 cells) was detected by western blotting. EdU/DAPI was used to evaluate the proliferation of EoL-1 cells. A CRS model was established using Gαi1/3-knockout mice, and histological analysis and inflammatory cytokine measurements were performed. Results: Compared with the non-eCRS subset, the eCRS subset showed significantly increased Gαi1/3 expression levels. High nasal tissue Gαi1/3 levels were linked to high tissue eosinophil infiltration, and high disease severity and allergic conditions in CRS patients. Gαi1/3 were required for IL-5-induced Akt-mTOR and Erk activation in MEFs. In EoL-1 cells, Gαi1/3 was associated with IL-5-activated IL-5Rα, promoting IL-5Rα endocytosis and transducing downstream signaling. IL-5-induced EoL-1 cell proliferation and degranulation were suppressed after Gαi1/3 silencing. In a CRS murine model, immune cell infiltration and type 2 inflammation were largely impaired in Gαi1/3-double-knockout mice. Conclusion: Increased Gαi1/3 expression levels in nasal tissue are linked to eosinophil infiltration and increased disease severity in CRS patients. Gαi1/3 contributes to eosinophil activation and participates in regulating allergic inflammation in CRS patients. [ABSTRACT FROM AUTHOR]

Background: Galectin‐9 (Gal‐9) has been implicated in allergic and autoimmune diseases, but its role and relevance in chronic spontaneous urticaria (CSU) are unclear. Objectives: To characterize the role and relevance of Gal‐9 in the pathogenesis of CSU. Methods: We assessed 60 CSU patients for their expression of Gal‐9 on circulating eosinophils and basophils as well as T cell expression of the Gal‐9 receptor TIM‐3, compared them with 26 healthy controls (HCs), and explored possible links with disease features including disease activity (urticaria activity score, UAS), total IgE, basophil activation test (BAT), and response to omalizumab treatment. We also investigated potential drivers of Gal‐9 expression by eosinophils and basophils. Results: Our CSU patients had markedly increased rates of circulating Gal‐9+ eosinophils and basophils and high numbers of lesional Gal‐9+ cells. High rates of blood Gal‐9+ eosinophils/basophils were linked to high disease activity, IgE levels, and BAT negativity. Serum levels of TNF‐α were positively correlated with circulating Gal‐9+ eosinophils/basophils, and TNF‐α markedly upregulated Gal‐9 on eosinophils. CSU patients who responded to omalizumab treatment had more Gal‐9+ eosinophils/basophils than non‐responders, and omalizumab reduced blood levels of Gal‐9+ eosinophils/basophils in responders. Gal‐9+ eosinophils/basophils were negatively correlated with TIM‐3+TH17 cells. Conclusion: Our findings demonstrate a previously unrecognized involvement of the Gal‐9/TIM‐3 pathway in the pathogenesis CSU and call for studies that explore its relevance. [ABSTRACT FROM AUTHOR]

This article explores the relationship between basophil and eosinophil recruitment to skin lesions and autoimmune chronic spontaneous urticaria (CSU). The study reveals that CSU patients have increased levels of basophils and eosinophils in both lesional and non-lesional skin compared to healthy individuals. The numbers of these cells in the lesional skin are linked to disease activity and quality of life impairment. Furthermore, patients with low total IgE levels have higher levels of basophils and eosinophils in their lesional skin. Another study examines the connection between basophil and eosinophil counts in the blood and skin of CSU patients. It finds that patients with serum autoreactivity, indicated by a positive basophil activation test (BAT+), have higher levels of eosinophils in their skin lesions compared to BAT- patients. Additionally, BAT+ patients have lower blood counts of basophils and eosinophils, suggesting that their infiltration into the skin reduces their levels in the blood. The study emphasizes the need for further research on the role of these cells in CSU and the development of therapies targeting their recruitment and effects. [Extracted from the article]

Mast cells (MCs) are considered as key effector cells in the elicitation of allergic symptoms, and they are essential players in innate and adaptive immune responses. In mice, two main types of MCs have been described: connective tissue MCs (CTMCs) and mucosal MCs (MMCs). However, little is known about the biological functions of MMCs, which is due to the lack of suitable models to investigate MMCs in vivo. Here, we aimed to generate a mouse model selectively deficient in MMCs. It has been previously described that Cre expressed under the control of the baboon α-chymase promotor is predominantly localized in MMCs. Therefore, we mated α-chymase-Cre transgenic mice with mice bearing a floxed allele of the myeloid cell leukemia sequence 1 (Mcl-1). Mcl-1 encodes for an intracellular antiapoptotic factor in MCs; hence, a selective reduction in MMCs was expected. Our results show that this new mouse model contains markedly reduced numbers of MMCs in mucosal tissues, whereas numbers of CTMCs are normal. Thus, Chm-Cre; Mcl-1fl/fl mice are a useful tool for the investigation of the pathophysiological functions of MMCs in vivo. [ABSTRACT FROM AUTHOR]

The article explores the causal relationship between chronic spontaneous urticaria (CSU) and thyroid function indicators in different ethnic groups using Mendelian randomization analysis. The study found a genetic susceptibility to thyroid dysfunction associated with CSU in Europeans but not in Asians, with no evidence of reverse causation. The research suggests new avenues for investigating the link between thyroid autoimmunity and CSU, highlighting the need for future studies with larger and more diverse cohorts to refine our understanding of these mechanisms. [Extracted from the article]

Background: Chronic rhinosinusitis (CRS) is a chronic inflammatory disease with an autoimmune background. Altered expression levels of T cell immunoglobulin and mucin-domain containing-3 (TIM-3), C-X-C chemokine receptor type 5 (CXCR5), and programmed cell death protein 1 (PD-1) are implicated in the progression of inflammatory and autoimmune diseases. Moreover, CXCR5 + TIM-3 - PD-1 + stem-like cytotoxic T cells function as memory stem cells during chronic disease processes and retain cytotoxicity-related gene networks., Objectives: To explore the expressions of CXCR5, TIM-3, and PD-1 on T cells and their correlation with clinical parameters in CRS., Methods: Flow cytometry was used to assess the expressions and co-expressions of CXCR5, TIM-3, and PD-1 on T cells in the tissues of the paranasal sinus and peripheral blood of patients with CRS as well as healthy controls. Immunofluorescence was used to assess the co-localization of TIM-3, CXCR5, and PD-1 with T cells. The disease severity of our patients with CRS was evaluated using the Lund-Mackay score. A complete blood count was also performed for the patients with CRS., Results: Expression levels of CXCR5 and PD-1 on T cells were significantly increased in the nasal tissues of patients with CRS. Compared with those in healthy controls, patients with CRS had high percentages of CXCR5 + TIM-3 - PD-1 + CD8 + and CD4 + T cells in nasal tissues, while no significant difference was observed in peripheral blood levels. Patients with CRS had a higher density of nasal CXCR5+TIM-3-PD-1+ T cells than that in healthy controls. CXCR5 + TIM-3 - PD-1 + CD8 + T cell levels in the nasal polyps of patients with CRS were negatively correlated with the patients' Lund-Mackay scores. The levels of CXCR5 + TIM-3 - PD-1 + T cells in nasal tissues were also negatively associated with disease duration and positively associated with the chronic inflammatory state of CRS., Conclusions: The level of CXCR5 + TIM-3 - PD-1 + stem cell-like T cells, especially CXCR5+TIM-3-PD-1+ CD8+ T cells, is increased in CRS. Therefore, inducing CXCR5 + TIM-3 - PD-1 + T cell exhaustion may be an effective immunotherapy for CRS., 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 Liu, Zhao, Xie, Lu, Liu and Jiao.)