Transcriptional regulation of Th17 cell differentiation.
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.
Ivanov
Ivaylo I
II
The Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine, New York University School of Medicine and New York, NY 10016, United States.
Zhou
Liang
L
Littman
Dan R
DR
D000818:Animals; D002454:Cell Differentiation; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D050835:Interferon Regulatory Factors / Q000378:metabolism*; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism*; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D011988:Receptors, Thyroid Hormone / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D014158:Transcription, Genetic; D000099218:Interferon Regulatory Factor-4
D016207:Cytokines; D051858:Forkhead Transcription Factors; D050835:Interferon Regulatory Factors; D020381:Interleukin-17; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D000099218:Interferon Regulatory Factor-4; C539900:RORC protein, human; C539901:Rorc protein, mouse