title: Induction and molecular signature of pathogenic TH17 cells.
abstract: Interleukin 17 (IL-17)-producing helper T cells (T(H)17 cells) are often present at the sites of tissue inflammation in autoimmune diseases, which has led to the conclusion that T(H)17 cells are main drivers of autoimmune tissue injury. However, not all T(H)17 cells are pathogenic; in fact, T(H)17 cells generated with transforming growth factor-β1 (TGF-β1) and IL-6 produce IL-17 but do not readily induce autoimmune disease without further exposure to IL-23. Here we found that the production of TGF-β3 by developing T(H)17 cells was dependent on IL-23, which together with IL-6 induced very pathogenic T(H)17 cells. Moreover, TGF-β3-induced T(H)17 cells were functionally and molecularly distinct from TGF-β1-induced T(H)17 cells and had a molecular signature that defined pathogenic effector T(H)17 cells in autoimmune disease.
authors.affiliation: Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Youjin
authors.initials: Y
authors.lastname: Lee
authors.forename: Amit
authors.initials: A
authors.lastname: Awasthi
authors.forename: Nir
authors.initials: N
authors.lastname: Yosef
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Quintana
authors.forename: Sheng
authors.initials: S
authors.lastname: Xiao
authors.forename: Anneli
authors.initials: A
authors.lastname: Peters
authors.forename: Chuan
authors.initials: C
authors.lastname: Wu
authors.forename: Markus
authors.initials: M
authors.lastname: Kleinewietfeld
authors.forename: Sharon
authors.initials: S
authors.lastname: Kunder
authors.forename: David A
authors.initials: DA
authors.lastname: Hafler
authors.forename: Raymond A
authors.initials: RA
authors.lastname: Sobel
authors.forename: Aviv
authors.initials: A
authors.lastname: Regev
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Kuchroo
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology; D020381:Interleukin-17 / Q000096:biosynthesis*; D053759:Interleukin-23 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D051379:Mice; D058504:Th17 Cells / Q000276:immunology*; D053773:Transforming Growth Factor beta1 / Q000276:immunology* / Q000378:metabolism; D053782:Transforming Growth Factor beta3 / Q000276:immunology* / Q000378:metabolism
chemical_list: D020381:Interleukin-17; D053759:Interleukin-23; D015850:Interleukin-6; D053773:Transforming Growth Factor beta1; D053782:Transforming Growth Factor beta3