Immunity. 2006 Feb;24(2):179-89.

TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells.

Veldhoen M, Hocking RJ, Atkins CJ, Locksley RM, Stockinger B.

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Division of Molecular Immunology, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, United Kingdom.

Abstract

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 TGFbeta1, which, together with the proinflammatory cytokine IL-6, supports the differentiation of IL-17-producing T cells, a process that is amplified by IL-1beta and TNFalpha. 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 TGFbeta signaling, Smad7. Our data indicate that, in the presence of IL-6, TGFbeta1 subverts Th1 and Th2 differentiation for the generation of IL-17-producing T cells.

PMID:: 16473830; [PubMed - indexed for MEDLINE]

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