[PDF][PDF] TGFβ in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells

M Veldhoen, RJ Hocking, CJ Atkins, RM Locksley… - Immunity, 2006 - cell.com
M Veldhoen, RJ Hocking, CJ Atkins, RM Locksley, B Stockinger
Immunity, 2006cell.com
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 TGFβ1, which, together
with the proinflammatory cytokine IL-6, supports the differentiation of IL-17-producing T cells,
a process that is amplified by IL-1β and TNFα. 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 …
Summary
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 TGFβ1, which, together with the proinflammatory cytokine IL-6, supports the differentiation of IL-17-producing T cells, a process that is amplified by IL-1β and TNFα. 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 TGFβ signaling, Smad7. Our data indicate that, in the presence of IL-6, TGFβ1 subverts Th1 and Th2 differentiation for the generation of IL-17-producing T cells.
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