The phosphatase DUSP2 controls the activity of the transcription activator STAT3 and regulates [T.sub.H]17 differentiation

Deregulation of the [T.sub.H]17 subset of helper T cells is closely linked with immunological disorders and inflammatory diseases. However, the mechanism by which [T.sub.H]17 cells are regulated remains elusive. Here we found that the phosphatase DUSP2 (PACI) negatively regulated the development of [T.sub.H]17 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 [T.sub.H]17 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 [T.sub.H]17 cells in the autoimmune response and inflammation.