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         description:Interleukin 17 (IL-17)–producing T helper 17 cells (TH-17 cells) have been described as a T helper cell subset distinct from T helper type 1 (TH1) and TH2 cells, with specific functions in antimicrobial defense and autoimmunity. The factors driving human TH-17 differentiation remain controversial. Using a systematic approach combining experimental and computational methods, we show here that transforming growth factor-β, interleukin 23 (IL-23) and proinflammatory cytokines (IL-1β and IL-6) were all essential for human TH-17 differentiation. However, individual TH-17 cell–derived cytokines, such as IL-17, IL-21, IL-22 and IL-6, as well as the global TH-17 cytokine profile, were differentially modulated by TH-17-promoting cytokines. Transforming growth factor-β was critical, and its absence induced a shift from a TH-17 profile to a TH1-like profile. Our results shed new light on the regulation of human TH-17 differentiation and provide a framework for the global analysis of T helper responses.
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            name:Ecole des Mines de Paris
            address:
               name:Ecole des Mines de Paris, Fontainebleau, France
               type:PostalAddress
            type:Organization
      name:Vassili Soumelis
      affiliation:
            name:Institut National de la Santé et de la Recherche Médicale U653
            address:
               name:Institut National de la Santé et de la Recherche Médicale U653, Paris, France
               type:PostalAddress
            type:Organization
            name:Institut Curie, Laboratoire d'Immunologie Clinique
            address:
               name:Institut Curie, Laboratoire d'Immunologie Clinique, Paris, France
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Institut National de la Santé et de la Recherche Médicale U653, Paris, France
      name:Institut Curie, Laboratoire d'Immunologie Clinique, Paris, France
      name:Institut Curie, Bioinformatique, Paris, France
      name:Institut National de la Santé et de la Recherche Médicale, U900, Paris, France
      name:Ecole des Mines de Paris, Fontainebleau, France
      name:Institut National de la Santé et de la Recherche Médicale U653, Paris, France
      name:Institut Curie, Laboratoire d'Immunologie Clinique, Paris, France
      name:Institut National de la Santé et de la Recherche Médicale U653, Paris, France
      name:Institut Curie, Laboratoire d'Immunologie Clinique, Paris, France
      name:Institut Curie, Bioinformatique, Paris, France
      name:Institut National de la Santé et de la Recherche Médicale, U900, Paris, France
      name:Ecole des Mines de Paris, Fontainebleau, France
      name:Centre National de la Recherche Scientifique, UMR144, Paris, France
      name:Institut Curie, Bioinformatique, Paris, France
      name:Institut National de la Santé et de la Recherche Médicale, U900, Paris, France
      name:Ecole des Mines de Paris, Fontainebleau, France
      name:Institut National de la Santé et de la Recherche Médicale U653, Paris, France
      name:Institut Curie, Laboratoire d'Immunologie Clinique, Paris, France
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