In vivo equilibrium of proinflammatory IL-17+ and regulatory IL-10+ Foxp3+ RORγt+ T cells

M Lochner, L Peduto, M Cherrier, S Sawa… - The Journal of …, 2008 - rupress.org
M Lochner, L Peduto, M Cherrier, S Sawa, F Langa, R Varona, D Riethmacher, M Si-Tahar
The Journal of experimental medicine, 2008rupress.org
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 …
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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