title: T helper 17 cell heterogeneity and pathogenicity in autoimmune disease.
abstract: T helper (Th)17 cells have been proposed to represent a new CD4(+) T cell lineage that is important for host defense against fungi and extracellular bacteria, and the development of autoimmune diseases. Precisely how these cells arise has been the subject of some debate, with apparent species-specific differences in mice and humans. Here, we describe evolving views of Th17 specification, highlighting the contribution of transforming growth factor-β and the opposing roles of signal transducer and activator of transcription (STAT)3 and STAT5. Increasing evidence points to heterogeneity and inherent phenotypic instability in this subset. Ideally, better understanding of expression and action of key transcription factors and the epigenetic landscape of Th17 can help explain the flexibility and diversity of interleukin-17-producing cells.
authors.affiliation: Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Kamran
authors.initials: K
authors.lastname: Ghoreschi
authors.forename: Arian
authors.initials: A
authors.lastname: Laurence
authors.forename: Xiang-Ping
authors.initials: XP
authors.lastname: Yang
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hirahara
authors.forename: John J
authors.initials: JJ
authors.lastname: O'Shea
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000473:pathology* / Q000503:physiopathology; D001424:Bacterial Infections / Q000276:immunology* / Q000382:microbiology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology; D014644:Genetic Variation / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics; D020381:Interleukin-17 / Q000096:biosynthesis / Q000276:immunology*; D053760:Interleukin-23 Subunit p19 / Q000096:biosynthesis / Q000276:immunology*; D051379:Mice; D009181:Mycoses / Q000276:immunology* / Q000382:microbiology; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000276:immunology / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000276:immunology / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D013045:Species Specificity; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism
chemical_list: C508841:Il23a protein, mouse; D020381:Interleukin-17; D053760:Interleukin-23 Subunit p19; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; D016212:Transforming Growth Factor beta