TGFβ in the Context of an Inflammatory Cytokine Milieu Supports De Novo Differentiation of IL-17-Producing T Cells
ImmunityPublished 1 February 2006Open access
Marc Veldhoen, Richard J. Hocking, Christopher J. Atkins, Richard M. Locksley, Brigitta Stockinger
Citations3,575
SJR quartileQ1
SJR score12.16
SNIP4.01
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TL;DR
The data indicate that, in the presence of IL-6, TGFbeta1 subverts Th1 and Th2 differentiation for the generation ofIL-17-producing T cells.
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.
Keywords
Immunology and Microbiology
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