Caspase-1 inhibitor regulates humoral responses in experimental autoimmune myasthenia gravis via IL-6-dependent inhibiton of STAT3
Caspase-1 inhibitor regulates humoral responses in experimental autoimmune myasthenia gravis via IL-6-dependent inhibiton of STAT3
复制标题
Caspase-1 抑制剂通过 IL-6 依赖性抑制 STAT3 调节实验性自身免疫性重症肌无力的体液反应
DOI：
10.1016/j.neulet.2017.05.040
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发表时间：
2017
影响因子：
2.5
通讯作者：
Duan Rui-Sheng
中科院分区：
文献类型：
--
作者：
Wang Cong-Cong;Zhang Min;Li Heng;Li Xiao-Li;Yue Long-Tao;Zhang Peng;Liu Ru-Tao;Chen Hui;Li Yan-Bin;Duan Rui-Sheng
我们先前已经证明半胱氨酰丙氨酸特异性蛋白酶-1（caspase-1）抑制剂通过抑制DC IL-1 β、CD 4 +T和γdT细胞IL-17通路抑制细胞免疫应答来改善实验性自身免疫性重症肌无力（EAMG）。本研究旨在观察caspase-1抑制剂对EAMG体液免疫应答的影响，并进一步探讨其作用机制。用大鼠AChR α亚基97-116区（R97-116肽）诱导刘易斯大鼠MG动物模型。大鼠腹腔内（i. p.）从第一次免疫后第13天起每隔一天。采用流式细胞术、免疫印迹、免疫荧光和酶联免疫吸附试验（ELISA）等方法，观察caspase-1抑制剂对EAMG体液免疫反应的保护作用。结果表明，caspase-1抑制剂降低抗R97 -116 IgG的相对亲和力，抑制生发中心反应，减少滤泡辅助性T细胞，增加滤泡调节性T细胞和调节性B细胞。此外，我们发现caspase-1抑制剂通过抑制IL-6-STAT 3-Bcl-6途径抑制EAMG大鼠的体液免疫反应。这些结果表明，caspase-1抑制剂通过调节体液免疫反应来改善EAMG，从而为重症肌无力和其他自身免疫性疾病的治疗提供了新的见解。
We have previously demonstrated that Cysteinyl aspartate-specific proteinase-1 (caspase-1) inhibitor ameliorates experimental autoimmune myasthenia gravis (EAMG) by inhibited cellular immune response, via suppressing DC IL-1 β, CD4+T and γdT cells IL-17 pathways. In this study, we investigated the effect of caspase-1 inhibitor on humoral immune response of EAMG and further explore the underlying mechanisms. An animal model of MG was induced by region 97–116 of the rat AChR α subunit (R97-116 peptide) in Lewis rats. Rats were treated with caspase-1 inhibitor Ac-YVAD-cmk intraperitoneally (i.p.) every second day from day 13 after the first immunization. Flow cytometry, western blot, immunofluorescence, and enzyme-linked immunosorbent assay (ELISA) were performed to evaluate the neuroprotective effect of caspase-1 inhibitor on humoral immune response of EAMG. The results showed that caspase-1 inhibitor reduced the relative affinity of anti-R97-116 IgG, suppressed germinal center response, decreased follicular helper T cells, and increased follicular regulatory T cells and regulatory B cells. In addition, we found that caspase-1 inhibitor inhibited humoral immunity response in EAMG rats via suppressing IL-6-STAT3-Bcl-6 pathways. These results suggest that caspase-1 inhibitor ameliorates EAMG by regulating humoral immune response, thus providing new insights into the development of myasthenia gravis and other autoimmune diseases therapies.