IL‐37 attenuates allergic process via STAT6/STAT3 pathways in murine allergic rhinitis

Abstract

&NA; Allergic rhinitis (AR) is a common upper airway allergic disease caused by allergens triggering a type 2 immune response. The imbalance of CD4+ T cell subsets is the essential immunological feature of AR, which is mainly characterized by the predominance of T helper (Th) 2 cells. Recent studies indicated that the anti‐inflammatory factor interleukin (IL)‐37 is involved in the immune regulation of AR. However, the mechanism of IL‐37 acts on AR has not been fully elucidated. Thus, we sought to assess the protective role of IL‐37 in AR and further explore the possible mechanism. An ovalbumin (OVA)‐induced AR murine model was established. After IL‐37 treatment, the allergic symptoms (sneezes and nasal rubbings), nasal mucosal infiltration with eosinophils, and serum IgE production were found significantly attenuated. For CD4+ T cell subsets, the proliferation and differentiation of Th2 and Th17 cells were restrained. The relevant effector cytokines of IL‐4, IL‐5, IL‐6, and IL‐17a protein expression and transcription factors GATA3 and ROR&ggr;t mRNA levels were obviously decreased. However, IL‐37 had no significant effect on Th1 and Treg response including in IFN‐&ggr;, IL‐10, T‐bet, and Foxp3 expression. Furthermore, IL‐37 was found down‐regulated the STAT6, STAT3, phospho‐STAT6, and phospho‐STAT3 expression. In conclusion, IL‐37 alleviates allergic inflammation in AR possibly through repressing STAT6 and STAT3 signaling pathways.