Abstract
Distinct classes of protective immunity are guided by activation of STAT transcription factor family members in response to environmental cues. CD4+ regulatory T cells (T(regs)) suppress excessive immune responses, and their deficiency results in a lethal, multi-organ autoimmune syndrome characterized by T helper 1 (TH1) and T helper 2 (TH2) CD4+ T cell-dominated lesions. Here we show that pathogenic TH17 responses in mice are also restrained by T(regs). This suppression was lost upon T(reg)-specific ablation of Stat3, a transcription factor critical for TH17 differentiation, and resulted in the development of a fatal intestinal inflammation. These findings suggest that T(regs) adapt to their environment by engaging distinct effector response-specific suppression modalities upon activation of STAT proteins that direct the corresponding class of the immune response.
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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Cell Lineage
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Cytokines / metabolism
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Female
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Forkhead Transcription Factors / genetics
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Forkhead Transcription Factors / metabolism
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Inflammatory Bowel Diseases / immunology*
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Inflammatory Bowel Diseases / metabolism
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Inflammatory Bowel Diseases / pathology
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Interferon-gamma / metabolism
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Interleukin-17 / metabolism
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Intestine, Large / immunology
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Intestine, Large / pathology
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Lymph Nodes / immunology
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Lymph Nodes / pathology
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Lymphocyte Activation
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Male
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Mice
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Mice, Inbred C57BL
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Phosphorylation
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Receptors, CCR6 / genetics
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Receptors, CCR6 / metabolism
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STAT3 Transcription Factor / genetics
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STAT3 Transcription Factor / metabolism*
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Spleen / immunology
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Spleen / pathology
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T-Lymphocyte Subsets / immunology*
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T-Lymphocytes, Helper-Inducer / immunology*
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T-Lymphocytes, Regulatory / immunology*
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T-Lymphocytes, Regulatory / metabolism
Substances
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CCR6 protein, mouse
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Cytokines
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Forkhead Transcription Factors
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Foxp3 protein, mouse
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Interleukin-17
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Receptors, CCR6
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STAT3 Transcription Factor
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Stat3 protein, mouse
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Interferon-gamma