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

Matthias Lochner, Lucie Peduto, Marie Cherrier, Shinichiro Sawa, Francina Langa, Rosa Varona, Dieter Riethmacher, Mustapha Si-Tahar, James P. Di Santo, Gérard Eberl

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356 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1381-1393
Number of pages13
JournalJournal of Experimental Medicine
Volume205
Issue number6
DOIs
Publication statusPublished - Jun 9 2008

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Lochner, M., Peduto, L., Cherrier, M., Sawa, S., Langa, F., Varona, R., Riethmacher, D., Si-Tahar, M., Di Santo, J. P., & Eberl, G. (2008). In vivo equilibrium of proinflammatory IL-17+ and regulatory IL-10+ Foxp3+ RORγt+ T cells. Journal of Experimental Medicine, 205(6), 1381-1393. https://doi.org/10.1084/jem.20080034