New complexities in helper T cell fate determination and the implications for autoimmune diseases.
Recently, new complexities in cell fate decision for helper T cells have emerged. One new lineage, which has come to be called Th17 cells, selectively produces proinflammatory cytokines including interleukin-17 (IL-17, A and F), IL-21, and IL-22. In conjunction with transforming growth factor beta-1 (TGFbeta-1), IL-6, IL-21, and IL-23, which activate the transcription factor, signal transducer, and activator of transcription 3 (Stat3), the expression of another transcription factor, retinoic acid-related orphan receptor-gammat (RORgammat) leads to the differentiation of Th17 cells in mice. Other cytokines including IL-2, IL-4, interferon-gamma (IFN-gamma), and IL-27 inhibit Th17 differentiation. However, IL-2 acting with TGFbeta-1 induces differentiation of naïve CD4+ T cells to become regulatory T cells (Tregs). Th17 cells are now known to play an important role not only in the pathogenesis of inflammation and autoimmune diseases, but also host defense against extracellular bacteria. Conversely, extensive data substantiate the role of Tregs as essential in maintenance of peripheral tolerance. Selectively targeting Tregs and Th17 cells are likely to be important strategies in the treatment of inflammatory and autoimmune diseases in humans.
Takatori
Hiroaki
H
Lymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA. takatorih@mail.nih.gov
Kanno
Yuka
Y
Chen
Zhi
Z
O'Shea
John J
JJ
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D050796:STAT3 Transcription Factor / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D020381:Interleukin-17; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C539900:RORC protein, human; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; C539901:Rorc protein, mouse; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human