title: Late developmental plasticity in the T helper 17 lineage.
abstract: Development of T helper (Th) 17 cells requires transforming growth factor (TGF)-beta and interleukin (IL)-6 and is independent of the Th1 pathway. Although T cells that produce interferon (IFN)-gamma are a recognized feature of Th17 cell responses, mice deficient for STAT4 and T-bet-two prototypical Th1 transcription factors-are protected from autoimmunity associated with Th17 pathogenesis. To examine the fate and pathogenic potential of Th17 cells and origin of IFN-gamma-producing T cells that emerge during Th17 immunity, we developed IL-17F reporter mice that identify cells committed to expression of IL-17F and IL-17A. Th17 cells required TGF-beta for sustained expression of IL-17F and IL-17A. In the absence of TGF-beta, both IL-23 and IL-12 acted to suppress IL-17 and enhance IFN-gamma production in a STAT4- and T-bet-dependent manner, albeit with distinct efficiencies. These results support a model of late Th17 developmental plasticity with implications for autoimmunity and host defense.
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Yun Kyung
authors.initials: YK
authors.lastname: Lee
authors.forename: Henrietta
authors.initials: H
authors.lastname: Turner
authors.forename: Craig L
authors.initials: CL
authors.lastname: Maynard
authors.forename: James R
authors.initials: JR
authors.lastname: Oliver
authors.forename: Dongquan
authors.initials: D
authors.lastname: Chen
authors.forename: Charles O
authors.initials: CO
authors.lastname: Elson
authors.forename: Casey T
authors.initials: CT
authors.lastname: Weaver
mesh_terms: D000818:Animals; D019070:Cell Lineage / Q000276:immunology*; D002478:Cells, Cultured; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism*; D053759:Interleukin-23 / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D020381:Interleukin-17; D053759:Interleukin-23; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma