title: The phosphatase DUSP2 controls the activity of the transcription activator STAT3 and regulates TH17 differentiation.
abstract: Deregulation of the TH17 subset of helper T cells is closely linked with immunological disorders and inflammatory diseases. However, the mechanism by which TH17 cells are regulated remains elusive. Here we found that the phosphatase DUSP2 (PAC1) negatively regulated the development of TH17 cells. DUSP2 was directly associated with the signal transducer and transcription activator STAT3 and attenuated its activity through dephosphorylation of STAT3 at Tyr705 and Ser727. DUSP2-deficient mice exhibited severe susceptibility to experimental colitis, with enhanced differentiation of TH17 cells and secretion of proinflammatory cytokines. In clinical patients with ulcerative colitis, DUSP2 was downregulated by DNA methylation and was not induced during T cell activation. Our data demonstrate that DUSP2 is a true STAT3 phosphatase that modulates the development of TH17 cells in the autoimmune response and inflammation.
authors.affiliation: Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Lu
authors.affiliation: Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.|Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Liu
authors.affiliation: Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Ji
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: Xuyang
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: Yunqiao
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: Michael A
authors.initials: MA
authors.lastname: McNutt
authors.affiliation: Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.|Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.|Peking-Tsinghua Center for Life Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Yin
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D003092:Colitis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology; D003093:Colitis, Ulcerative / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D019175:DNA Methylation / Q000276:immunology; D016264:Dextran Sulfate; D054641:Dual Specificity Phosphatase 2 / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology; D057809:HEK293 Cells; D006801:Humans; D015151:Immunoblotting; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010766:Phosphorylation / Q000276:immunology; D011485:Protein Binding / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000276:immunology* / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism; D014443:Tyrosine / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D050796:STAT3 Transcription Factor; D014443:Tyrosine; D016264:Dextran Sulfate; D054641:Dual Specificity Phosphatase 2; C517033:Dusp2 protein, mouse