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         headline:Induction and molecular signature of pathogenic TH17 cells
         description:Exposure to interleukin 23 (IL-23) is required for the induction of pathogenic TH17 cells. Kuchroo and colleagues show that IL-23-dependent induction of the cytokine TGF-β3 produces a molecular signature characteristic of highly pathogenic TH17 cells. Interleukin 17 (IL-17)-producing helper T cells (TH17 cells) are often present at the sites of tissue inflammation in autoimmune diseases, which has led to the conclusion that TH17 cells are main drivers of autoimmune tissue injury. However, not all TH17 cells are pathogenic; in fact, TH17 cells generated with transforming growth factor-β1 (TGF-β1) and IL-6 produce IL-17 but do not readily induce autoimmune disease without further exposure to IL-23. Here we found that the production of TGF-β3 by developing TH17 cells was dependent on IL-23, which together with IL-6 induced very pathogenic TH17 cells. Moreover, TGF-β3-induced TH17 cells were functionally and molecularly distinct from TGF-β1-induced TH17 cells and had a molecular signature that defined pathogenic effector TH17 cells in autoimmune disease.
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            address:
               name:Broad Institute of MIT and Harvard, Cambridge, USA
               type:PostalAddress
            type:Organization
            name:Howard Hughes Medical Institute, Massachusetts Institute of Technology
            address:
               name:Department of Biology, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, USA
               type:PostalAddress
            type:Organization
      name:Vijay K Kuchroo
      affiliation:
            name:Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School
            address:
               name:Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, USA
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, USA
      name:Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, USA
      name:Present address: Translational Health Science & Technology Institute, Faridabad, Haryana, India.,
      name:Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, USA
      name:Broad Institute of MIT and Harvard, Cambridge, USA
      name:Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, USA
      name:Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, USA
      name:Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, USA
      name:Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, USA
      name:Department of Neurology, Yale University School of Medicine, New Haven, USA
      name:Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, USA
      name:Department of Neurology, Yale University School of Medicine, New Haven, USA
      name:Palo Alto Veteran's Administration Health Care System and Department of Pathology, Stanford University School of Medicine, Stanford, USA
      name:Broad Institute of MIT and Harvard, Cambridge, USA
      name:Department of Biology, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, USA
      name:Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, USA
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