Transcriptional regulation of Th17 cell differentiation

Semin Immunol. 2007 Dec;19(6):409-17. doi: 10.1016/j.smim.2007.10.011. Epub 2007 Nov 28.


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

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Differentiation
  • Cytokines / immunology
  • Cytokines / metabolism*
  • Forkhead Transcription Factors / metabolism*
  • Humans
  • Interferon Regulatory Factors / metabolism*
  • Interleukin-17 / immunology
  • Interleukin-17 / metabolism*
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Receptors, Retinoic Acid / metabolism*
  • Receptors, Thyroid Hormone / metabolism*
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes, Helper-Inducer / cytology
  • T-Lymphocytes, Helper-Inducer / immunology
  • T-Lymphocytes, Helper-Inducer / metabolism*
  • Transcription, Genetic


  • Cytokines
  • Forkhead Transcription Factors
  • Interferon Regulatory Factors
  • Interleukin-17
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • RORC protein, human
  • Receptors, Retinoic Acid
  • Receptors, Thyroid Hormone
  • Rorc protein, mouse
  • interferon regulatory factor-4