期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 45, 期 8, 页码 2377-2388出版社
WILEY-BLACKWELL
DOI: 10.1002/eji.201445349
关键词
Autophagy; B cells; Interferon-alpha; STS-1; Systemic lupus erythematosus
类别
资金
- National Natural Science Foundation [31370899]
- China postdoctoral science foundation [2013M531331]
- Scientific Research Foundation of Graduate School of Nanjing University [2013CL11]
- Ministry of Science
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the overexpression of IFN-alpha IFN-alpha induces autophagy via the JAK1-STAT1 signaling pathway, contributing to the pathogenesis of SLE. Recent studies reported that B cells from patients with SLE and NZBM Fl mice had enhanced autophagy activity; however, the mechanism still remains unknown. Here, we show that the protein tyrosine phosphatase STS-1 (suppressor of T-cell receptor signaling 1) was significantly overexpressed in B cells from patients with SLE and MRL/Ipr mice. Notably, STS-1 promoted IFN-alpha-induced autophagy in B cells by enhancing the JAK1-STAT1 signaling activation. STS-1 inhibited the phosphorylation of the E3 ubiquitin protein ligase c-cbl, and subsequently promoted IFN-ainduced phosphorylation of tyrosine kinase 2, leading to JAK1-STAT1 signaling activation. Furthermore, STAT1 and JAK1 inhibitors blocked the IFN-a-induced autophagy promoted by STS-1, indicating that STS-1 promotes IFN-alpha-induced autophagy via the JAK1-STAT1 signaling. Our results demonstrate the importance of STS-1 in regulating IFN-alpha-induced autophagy in B cells, and this could be used as a therapeutic approach to treat SLE.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据