Abstract
The paradigm of effector T helper cell differentiation into either Th1 or Th2 lineages has been profoundly shaken by the discovery of T cells that secrete IL-17 and other inflammatory cytokines. This subset, referred to as Th17, is centrally involved in autoimmune disease and is important in host defense at mucosal surfaces. In mouse, a series of cytokines, including IL-6, IL-21, IL-23, and TGF-beta, function sequentially or synergistically to induce the Th17 lineage. Other cytokines, including IL-2, IL-4, IFNgamma, and IL-27, inhibit differentiation of this lineage. Here we review how the nuclear orphan receptor RORgammat functions to coordinate the diverse cytokine-induced signals and thus controls Th17 cell differentiation.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Cell Differentiation
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Cytokines / immunology
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Cytokines / metabolism*
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Forkhead Transcription Factors / metabolism*
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Humans
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Interferon Regulatory Factors / metabolism*
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Interleukin-17 / immunology
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Interleukin-17 / metabolism*
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Nuclear Receptor Subfamily 1, Group F, Member 3
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Receptors, Retinoic Acid / metabolism*
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Receptors, Thyroid Hormone / metabolism*
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T-Lymphocyte Subsets / cytology
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / metabolism
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T-Lymphocytes, Helper-Inducer / cytology
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T-Lymphocytes, Helper-Inducer / immunology
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T-Lymphocytes, Helper-Inducer / metabolism*
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Transcription, Genetic
Substances
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Cytokines
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Forkhead Transcription Factors
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Interferon Regulatory Factors
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Interleukin-17
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Nuclear Receptor Subfamily 1, Group F, Member 3
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RORC protein, human
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Receptors, Retinoic Acid
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Receptors, Thyroid Hormone
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Rorc protein, mouse
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interferon regulatory factor-4