title: STS-1 promotes IFN-α induced autophagy by activating the JAK1-STAT1 signaling pathway in B cells.
abstract: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the overexpression of IFN-α. IFN-α 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-α-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-α-induced phosphorylation of tyrosine kinase 2, leading to JAK1-STAT1 signaling activation. Furthermore, STAT1 and JAK1 inhibitors blocked the IFN-α-induced autophagy promoted by STS-1, indicating that STS-1 promotes IFN-α-induced autophagy via the JAK1-STAT1 signaling. Our results demonstrate the importance of STS-1 in regulating IFN-α-induced autophagy in B cells, and this could be used as a therapeutic approach to treat SLE.
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, China.
authors.forename: Guanjun
authors.initials: G
authors.lastname: Dong
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, China.
authors.forename: Ming
authors.initials: M
authors.lastname: You
authors.affiliation: State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.
authors.forename: Hongye
authors.initials: H
authors.lastname: Fan
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Ding
authors.affiliation: Department of Immunology and Rheumatology, The Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, China.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Sun
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, China.|Jiangsu Key Laboratory of Molecular Medicine, Nanjing, China.
authors.forename: Yayi
authors.initials: Y
authors.lastname: Hou
mesh_terms: D000818:Animals; D001343:Autophagy / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology*; D053613:Janus Kinase 1 / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000628:therapy; D008297:Male; D051379:Mice; D017027:Protein Tyrosine Phosphatases / Q000276:immunology*; D050721:Proto-Oncogene Proteins c-cbl / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D050794:STAT1 Transcription Factor / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D053634:TYK2 Kinase / Q000276:immunology
chemical_list: D016898:Interferon-alpha; D011948:Receptors, Antigen, T-Cell; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; C494080:Stat1 protein, mouse; D050721:Proto-Oncogene Proteins c-cbl; C507904:JAK1 protein, human; C507905:Jak1 protein, mouse; D053613:Janus Kinase 1; D053634:TYK2 Kinase; C070139:TYK2 protein, human; C499356:Tyk2 protein, mouse; D017027:Protein Tyrosine Phosphatases; C553497:TULA-2 protein, mouse; C489397:UBASH3B protein, human; C067419:CBL protein, human; C493849:Cbl protein, mouse
keywords: Autophagy ⋅ B cells ⋅ Interferon-α ⋅ STS-1 ⋅ Systemic lupus erythematosus