In vivo equilibrium of proinflammatory IL-17+ and regulatory IL-10+ Foxp3+ RORgamma t+ T cells.
The nuclear hormone receptor retinoic acid receptor-related orphan receptor gamma t (RORgamma t) is required for the generation of T helper 17 cells expressing the proinflammatory cytokine interleukin (IL)-17. In vivo, however, less than half of RORgamma t(+) T cells express IL-17. We report here that RORgamma t(+) T alphabeta cells include Foxp3(+) cells that coexist with IL-17-producing RORgamma t(+) T alphabeta cells in all tissues examined. The Foxp3(+) RORgamma t(+) T alphabeta express IL-10 and CCL20, and function as regulatory T cells. Furthermore, the ratio of Foxp3(+) to IL-17-producing RORgamma t(+) T alphabeta 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 RORgamma t(+) T cells express the gammadelta 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(+) RORgamma t(+) T cells coexist and are tightly controlled, suggesting that a perturbed equilibrium in RORgamma t(+) T cells might lead to decreased immunoreactivity or, in contrast, to pathological inflammation.
Lochner
Matthias
M
Laboratory of Lymphoid Tissue Development, Centre National de la Recherche Scientifique URA1961, Institut Pasteur, Paris 75724, France.
Peduto
Lucie
L
Cherrier
Marie
M
Sawa
Shinichiro
S
Langa
Francina
F
Varona
Rosa
R
Riethmacher
Dieter
D
Si-Tahar
Mustapha
M
Di Santo
James P
JP
Eberl
Gérard
G
D000818:Animals; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology*; D017930:Genes, Reporter; D014644:Genetic Variation; D007249:Inflammation / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology*; D020381:Interleukin-17 / Q000276:immunology*; D015850:Interleukin-6 / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D053707:Receptors, Interleukin-12 / Q000276:immunology; D018168:Receptors, Retinoic Acid / Q000276:immunology*; D011988:Receptors, Thyroid Hormone / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D020381:Interleukin-17; D015850:Interleukin-6; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D053707:Receptors, Interleukin-12; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; C539901:Rorc protein, mouse; D016753:Interleukin-10