IL-37 Represses the Autoimmunity in Myasthenia Gravis via Directly Targeting Follicular Th and B Cells
Zhuo Liu, Liwen Zhu, Zhengjuan Lu, Huiping Chen, Lizhen Fan, Qun Xue, Jian‐Quan Shi, Meiying Li, Hui Li, Jie Gong, Jingping Shi, Tao Wang, Meiling Jiang, Runjing Cao, Hailan Meng, Chenhui Wang, Yun Xu, Cun‐Jin Zhang
Abstract
Abstract IL-37 is a newly identified immune-suppressive factor; however, the function, cellular sources, and mechanism of IL-37 in humoral immunity and Myasthenia gravis (MG) are still unclear. In this study, we found IL-37 were substantially downregulated in the serum and PBMCs of MG patients compared with healthy controls. The lower IL-37 was associated with severer disease (quantitative MG score) and higher follicular Th (Tfh)/Tfh17 and B cell numbers. Flow cytometry analysis revealed that IL-37 was mainly produced by CD4+ T cells without overlapping with Th1, Th17, and Tfh subsets in MG patients. Regulatory IL-37+ T cell rarely expressed Foxp3 and CD25 but produced numerous IL-4. Tfh and B cell expressed high levels of SIGIRR, the receptor of IL-37, in MG patients. Mechanically, IL-37 directly bond to SIGIRR, repressed the proliferation, cytokine production of Tfh and B cells, and the secretion of autoantibody via inhibition of STAT3 signaling in Tfh and B cells.