Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid.
The cytokine transforming growth factor-beta (TGF-beta) converts naïve T cells into regulatory T (Treg) cells that prevent autoimmunity. However, in the presence of interleukin-6 (IL-6), TGF-beta has also been found to promote the differentiation of naïve T lymphocytes into proinflammatory IL-17 cytokine-producing T helper 17 (T(H)17) cells, which promote autoimmunity and inflammation. This raises the question of how TGF-beta can generate such distinct outcomes. We identified the vitamin A metabolite retinoic acid as a key regulator of TGF-beta-dependent immune responses, capable of inhibiting the IL-6-driven induction of proinflammatory T(H)17 cells and promoting anti-inflammatory Treg cell differentiation. These findings indicate that a common metabolite can regulate the balance between pro- and anti-inflammatory immunity.
Mucida
Daniel
D
La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
Park
Yunji
Y
Kim
Gisen
G
Turovskaya
Olga
O
Scott
Iain
I
Kronenberg
Mitchell
M
Cheroutre
Hilde
H
D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D003092:Colitis / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D003984:Dibenzazepines / Q000494:pharmacology; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D020381:Interleukin-17 / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology; D008088:Listeriosis / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013154:Spleen / Q000166:cytology / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology / Q000502:physiology*
D003984:Dibenzazepines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D020381:Interleukin-17; D007376:Interleukin-2; D015850:Interleukin-6; C104183:LE 540; D016212:Transforming Growth Factor beta; D014212:Tretinoin