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

• Published in: International immunopharmacology 2019-04, Vol.69, p.27-33
• Main Authors: Wang, Jue, Shen, Yang, Li, Cong, Liu, Chuan, Wang, Zhi-Hai, Li, Yan-Shi, Ke, Xia, Hu, Guo-Hua
• Format: Article
• Language: English
• Subjects: Allergens; Allergic diseases; Allergic rhinitis; Animal models; CD4 antigen; Cell proliferation; Cytokines; Eosinophils; Foxp3 protein; GATA-3 protein; Gene expression; Helper cells; Hypersensitivity; Immune response; Immune system; Immunoglobulin E; Immunology; Immunoregulation; Infiltration; Inflammation; Interleukin 10; Interleukin 4; Interleukin 5; Interleukin 6; Interleukin-37; Leukocytes (eosinophilic); Lymphocytes; Lymphocytes T; Mucosa; Nose; Ovalbumin; Proteins; Respiratory tract; Respiratory tract diseases; Rhinitis; Signs and symptoms; STAT3; Stat3 protein; STAT6; Th17; Th2; Transcription factors; γ-Interferon
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2019.01.013

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 RORγt mRNA levels were obviously decreased. However, IL-37 had no significant effect on Th1 and Treg response including in IFN-γ, 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. •Systemic application of IL-37 attenuates the allergic inflammatory response in allergic rhinitis mice.•IL-37 modulates the immune imbalance of CD4+ Th subsets by suppressing Th2 and Th17 response.•IL-37 regulates Th2 and Th17 response is associated with STAT6 and STAT3 signaling pathways.