STS-1 promotes IFN-α induced autophagy by activating the JAK1-STAT1 signaling pathway in B cells
STS-1 promotes IFN-α induced autophagy by activating the JAK1-STAT1 signaling pathway in B cells
复制标题
STS-1通过激活B细胞中的JAK1-STAT1信号通路促进IFN-α诱导的自噬
DOI：
10.1002/eji.201445349
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发表时间：
2015-08-01
影响因子：
5.4
通讯作者：
Hou, Yayi
中科院分区：
文献类型：
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作者：
Dong, Guanjun;You, Ming;Hou, Yayi
系统性红斑狼疮（SLE）是一种以ifn - α过表达为特征的自身免疫性疾病，ifn - α通过JAK1-STAT1信号通路诱导自噬，参与SLE的发病机制。最近的研究报道SLE患者和NZBM Fl小鼠的B细胞具有增强的自噬活性；然而，其机制尚不清楚。在这里，我们发现蛋白酪氨酸磷酸酶STS-1 （t细胞受体信号1的抑制因子）在SLE患者和MRL/Ipr小鼠的B细胞中显著过表达。值得注意的是，STS-1通过增强JAK1-STAT1信号通路激活，促进ifn - α诱导的B细胞自噬。STS-1抑制E3泛素蛋白连接酶c-cbl的磷酸化，随后促进ifn诱导的酪氨酸激酶2的磷酸化，导致JAK1-STAT1信号通路激活。此外，STAT1和JAK1抑制剂阻断了STS-1促进ifn - α诱导的自噬，表明STS-1通过JAK1-STAT1信号通路促进ifn - α诱导的自噬。我们的研究结果表明STS-1在调节ifn - α诱导的B细胞自噬中的重要性，这可以作为治疗SLE的一种治疗方法。
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.