IL-6 prevents Th2 cell polarization by promoting SOCS3-dependent suppression of IL-2 signaling  

作　　者：Holly Bachus Erin McLaughlin Crystal Lewis Amber M.Papillion Etty N.Benveniste Dave Durell Hill Alexander F.Rosenberg AndréBallesteros-Tato Beatriz León 

机构地区：[1]Department of Medicine,Division of Clinical Immunology and Rheumatology,University of Alabama at Birmingham,Birmingham,AL,USA [2]Department of Microbiology,University of Alabama at Birmingham,Birmingham,AL,USA [3]Department of Cell,Developmental and Integrative Biology,University of Alabama at Birmingham,Birmingham,AL,USA [4]informatics Institute,University of Alabama at Birmingham,Birmingham,AL,USA [5]Alexion Pharmaceuticals,Inc.,New Haven,CT,USA

出　　处：《Cellular & Molecular Immunology》2023年第6期651-665,共15页中国免疫学杂志（英文版）

摘　　要：Defective interleukin-6 (IL-6) signaling has been associated with Th2 bias and elevated IgE levels. However, the underlying mechanism by which IL-6 prevents the development of Th2-driven diseases remains unknown. Using a model of house dust mite (HDM)-induced Th2 cell differentiation and allergic airway inflammation, we showed that IL-6 signaling in allergen-specific T cells was required to prevent Th2 cell differentiation and the subsequent IgE response and allergic inflammation. Th2 cell lineage commitment required strong sustained IL-2 signaling. We found that IL-6 turned off IL-2 signaling during early T-cell activation and thus inhibited Th2 priming. Mechanistically, IL-6-driven inhibition of IL-2 signaling in responding T cells was mediated by upregulation of Suppressor Of Cytokine Signaling 3 (SOCS3). This mechanism could be mimicked by pharmacological Janus Kinase-1 (JAK1) inhibition. Collectively, our results identify an unrecognized mechanism that prevents the development of unwanted Th2 cell responses and associated diseases and outline potential preventive interventions.

关 键 词：Th2 cell polarization IL-6 IL-2 SOCS3 JAK1 inhibitor 

分 类 号：R392[医药卫生—免疫学]