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- Title
The differentiation of human T<sub>H</sub>-17 cells requires transforming growth factor-β and induction of the nuclear receptor RORγt.
- Authors
Manel, Nicolas; Unutmaz, Derya; Littman, Dan R
- Abstract
TH-17 cells are interleukin 17 (IL-17)–secreting CD4+ T helper cells involved in autoimmune disease and mucosal immunity. In naive CD4+ T cells from mice, IL-17 is expressed in response to a combination of IL-6 or IL-21 and transforming growth factor-β (TGF-β) and requires induction of the nuclear receptor RORγt. It has been suggested that the differentiation of human TH-17 cells is independent of TGF-β and thus differs fundamentally from that in mice. We show here that TGF-β, IL-1β and IL-6, IL-21 or IL-23 in serum-free conditions were necessary and sufficient to induce IL-17 expression in naive human CD4+ T cells from cord blood. TGF-β upregulated RORγt expression but simultaneously inhibited its ability to induce IL-17 expression. Inflammatory cytokines relieved this inhibition and increased RORγt-directed IL-17 expression. Other gene products detected in TH-17 cells after RORγt induction included the chemokine receptor CCR6, the IL-23 receptor, IL-17F and IL-26. Our studies identify RORγt as having a central function in the differentiation of human TH-17 cells from naive CD4+ T cells and suggest that similar cytokine pathways are involved in this process in mice and humans.
- Publication
Nature Immunology, 2008, Vol 9, Issue 6, p641
- ISSN
1529-2908
- Publication type
Academic Journal
- DOI
10.1038/ni.1610