TY - JOUR
T1 - In vivo equilibrium of proinflammatory IL-17+ and regulatory IL-10+ Foxp3+ RORγt+ T cells
AU - Lochner, Matthias
AU - Peduto, Lucie
AU - Cherrier, Marie
AU - Sawa, Shinichiro
AU - Langa, Francina
AU - Varona, Rosa
AU - Riethmacher, Dieter
AU - Si-Tahar, Mustapha
AU - Di Santo, James P.
AU - Eberl, Gérard
PY - 2008/6/9
Y1 - 2008/6/9
N2 - The nuclear hormone receptor retinoic acid receptor-related orphan receptor γt (RORγt) is required for the generation of T helper 17 cells expressing the proinflammatory cytokine interleukin (IL)-17. In vivo, however, less than half of RORγt+ T cells express IL-17. We report here that RORγt+ Tαβ cells include Foxp3+ cells that coexist with IL-17-producing RORγt+ Tαβ cells in all tissues examined. The Foxp3+ RORγt+ Tαβ express IL-10 and CCL20, and function as regulatory T cells. Furthermore, the ratio of Foxp3+ to IL-17-producing RORγt + Tαβ cells remains remarkably constant in mice enduring infection and inflammation. This equilibrium is tuned in favor of IL-10 production by Foxp3 and CCL20, and in favor of IL-17 production by IL-6 and IL-23. In the lung and skin, the largest population of RORγt+ T cells express the γδ T cell receptor and produce the highest levels of IL-17 independently of IL-6. Thus, potentially antagonistic proinflammatory IL-17-producing and regulatory Foxp3+ RORγt+ T cells coexist and are tightly controlled, suggesting that a perturbed equilibrium in RORγt+ T cells might lead to decreased immunoreactivity or, in contrast, to pathological inflammation.
AB - The nuclear hormone receptor retinoic acid receptor-related orphan receptor γt (RORγt) is required for the generation of T helper 17 cells expressing the proinflammatory cytokine interleukin (IL)-17. In vivo, however, less than half of RORγt+ T cells express IL-17. We report here that RORγt+ Tαβ cells include Foxp3+ cells that coexist with IL-17-producing RORγt+ Tαβ cells in all tissues examined. The Foxp3+ RORγt+ Tαβ express IL-10 and CCL20, and function as regulatory T cells. Furthermore, the ratio of Foxp3+ to IL-17-producing RORγt + Tαβ cells remains remarkably constant in mice enduring infection and inflammation. This equilibrium is tuned in favor of IL-10 production by Foxp3 and CCL20, and in favor of IL-17 production by IL-6 and IL-23. In the lung and skin, the largest population of RORγt+ T cells express the γδ T cell receptor and produce the highest levels of IL-17 independently of IL-6. Thus, potentially antagonistic proinflammatory IL-17-producing and regulatory Foxp3+ RORγt+ T cells coexist and are tightly controlled, suggesting that a perturbed equilibrium in RORγt+ T cells might lead to decreased immunoreactivity or, in contrast, to pathological inflammation.
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U2 - 10.1084/jem.20080034
DO - 10.1084/jem.20080034
M3 - Article
C2 - 18504307
AN - SCOPUS:45149109643
VL - 205
SP - 1381
EP - 1393
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
SN - 0022-1007
IS - 6
ER -