Key Points Reduced IL-37 was associated with the pathogenesis of MG. Tfh and B cells highly express IL-37 receptor SIGIRR. IL-37 represses the activation of Tfh and B cells via STAT3 signaling. 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.

中文翻译：

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IL-37 通过直接靶向滤泡 Th 和 B 细胞抑制重症肌无力的自身免疫

关键点 IL-37 的降低与 MG 的发病机制有关。Tfh 和 B 细胞高度表达 IL-37 受体 SIGIRR。IL-37 通过 STAT3 信号抑制 Tfh 和 B 细胞的激活。IL-37 是一种新发现的免疫抑制因子；然而，IL-37在体液免疫和重症肌无力（MG）中的功能、细胞来源和机制尚不清楚。在这项研究中，我们发现与健康对照相比，MG 患者的血清和 PBMC 中的 IL-37 显着下调。较低的 IL-37 与较严重的疾病（定量 MG 评分）和较高的滤泡 Th (Tfh)/Tfh17 和 B 细胞数量相关。流式细胞术分析显示 IL-37 主要由 CD4+ T 细胞产生，与 MG 患者的 Th1、Th17 和 Tfh 亚群不重叠。调节性 IL-37+ T 细胞很少表达 Foxp3 和 CD25，但会产生大量 IL-4。Tfh 和 B 细胞在 MG 患者中表达高水平的 SIGIRR，即 IL-37 的受体。在机械上，IL-37 直接与 SIGIRR 结合，通过抑制 Tfh 和 B 细胞中的 STAT3 信号传导抑制 Tfh 和 B 细胞的增殖、细胞因子产生以及自身抗体的分泌。