Abstract
Transcription factor Foxp3 is critical for generating regulatory T cells (T(reg) cells). Transforming growth factor-beta (TGF-beta) induces Foxp3 and suppressive T(reg) cells from naive T cells, whereas interleukin 6 (IL-6) inhibits the generation of inducible T(reg) cells. Here we show that IL-4 blocked the generation of TGF-beta-induced Foxp3(+) T(reg) cells and instead induced a population of T helper cells that produced IL-9 and IL-10. The IL-9(+)IL-10(+) T cells demonstrated no regulatory properties despite producing abundant IL-10. Adoptive transfer of IL-9(+)IL-10(+) T cells into recombination-activating gene 1-deficient mice induced colitis and peripheral neuritis, the severity of which was aggravated if the IL-9(+)IL-10(+) T cells were transferred with CD45RB(hi) CD4(+) effector T cells. Thus IL-9(+)IL-10(+) T cells lack suppressive function and constitute a distinct population of helper-effector T cells that promote tissue inflammation.
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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Adoptive Transfer
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Animals
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Cell Differentiation / immunology
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Forkhead Transcription Factors / immunology*
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Forkhead Transcription Factors / metabolism
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GATA3 Transcription Factor / immunology
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GATA3 Transcription Factor / metabolism
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Interleukin-10 / immunology
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Interleukin-10 / metabolism
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Interleukin-4 / immunology*
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Interleukin-4 / metabolism
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Interleukin-9 / immunology
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Interleukin-9 / metabolism
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Lymphocyte Activation / immunology
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Mice
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Mice, Transgenic
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STAT6 Transcription Factor / immunology
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STAT6 Transcription Factor / metabolism
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T-Lymphocyte Subsets / cytology
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T-Lymphocyte Subsets / immunology*
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T-Lymphocytes, Regulatory / cytology
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T-Lymphocytes, Regulatory / immunology*
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Transforming Growth Factor beta / immunology*
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Transforming Growth Factor beta / metabolism
Substances
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Forkhead Transcription Factors
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Foxp3 protein, mouse
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GATA3 Transcription Factor
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Gata3 protein, mouse
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Interleukin-9
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STAT6 Transcription Factor
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Transforming Growth Factor beta
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Interleukin-10
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Interleukin-4