TGF[beta] in the Context of an Inflammatory Cytokine Milieu Supports De Novo Differentiation of IL-17-Producing T Cells.
Veldhoen, Marc 1; Hocking, Richard J. 1; Atkins, Christopher J. 2; Locksley, Richard M. 3; Stockinger, Brigitta 1,∗
[Article] Immunity. 24(2):179-189, February 2006.

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: We describe de novo generation of IL-17-producing T cells from naive CD4 T cells, induced in cocultures of naive CD4 T cells and naturally occurring CD4 CD25 T cells (Treg) in the presence of TLR3, TLR4, or TLR9 stimuli. Treg can be substituted by TGF[beta]1, which, together with the proinflammatory cytokine IL-6, supports the differentiation of IL-17-producing T cells, a process that is amplified by IL-1[beta] and TNF[alpha]. We could not detect a role for IL-23 in the differentiation of IL-17-producing T cells but confirmed its importance for their survival and expansion. Transcription factors GATA-3 and T-bet, as well as its target Hlx, are absent in IL-17-producing T cells, and they do not express the negative regulator for TGF[beta] signaling, Smad7. Our data indicate that, in the presence of IL-6, TGF[beta]1 subverts Th1 and Th2 differentiation for the generation of IL-17-producing T cells.

(C) 2006Elsevier, Inc.