| First Author | Dong G | Year | 2015 |
| Journal | Eur J Immunol | Volume | 45 |
| Issue | 8 | Pages | 2377-88 |
| PubMed ID | 25959715 | Mgi Jnum | J:229755 |
| Mgi Id | MGI:5754429 | Doi | 10.1002/eji.201445349 |
| Citation | Dong G, et al. (2015) STS-1 promotes IFN-alpha induced autophagy by activating the JAK1-STAT1 signaling pathway in B cells. Eur J Immunol 45(8):2377-88 |
| abstractText | 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 NZB/W F1 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/lpr 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-alpha-induced phosphorylation of tyrosine kinase 2, leading to JAK1-STAT1 signaling activation. Furthermore, STAT1 and JAK1 inhibitors blocked the IFN-alpha-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. |
