Late developmental plasticity in the T helper 17 lineage.
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.
Lee
Yun Kyung
YK
Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Turner
Henrietta
H
Maynard
Craig L
CL
Oliver
James R
JR
Chen
Dongquan
D
Elson
Charles O
CO
Weaver
Casey T
CT
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*
D020381:Interleukin-17; D053759:Interleukin-23; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma