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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism
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Cell Differentiation
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Cells, Cultured
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Cytokines / metabolism*
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Dendritic Cells / immunology
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Interleukin-17 / biosynthesis*
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Lymphocyte Subsets / immunology*
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Membrane Glycoproteins / physiology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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Receptors, Interleukin-1 / physiology
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Smad7 Protein / metabolism
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T-Lymphocytes / immunology*
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T-Lymphocytes, Regulatory / immunology
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Th1 Cells / immunology
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Th2 Cells / immunology
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Transforming Growth Factor beta / physiology*
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Transforming Growth Factor beta1
Substances
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Cytokines
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Interleukin-17
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Membrane Glycoproteins
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Receptors, Interleukin-1
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Smad7 Protein
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TIRAP protein, mouse
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Tgfb1 protein, mouse
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Transforming Growth Factor beta
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Transforming Growth Factor beta1