Abstract
CD4(+) T regulatory cells (T(regs)), which express the Foxp3 transcription factor, play a critical role in the maintenance of immune homeostasis. Here, we show that in mice, T(regs) were most abundant in the colonic mucosa. The spore-forming component of indigenous intestinal microbiota, particularly clusters IV and XIVa of the genus Clostridium, promoted T(reg) cell accumulation. Colonization of mice by a defined mix of Clostridium strains provided an environment rich in transforming growth factor-β and affected Foxp3(+) T(reg) number and function in the colon. Oral inoculation of Clostridium during the early life of conventionally reared mice resulted in resistance to colitis and systemic immunoglobulin E responses in adult mice, suggesting a new therapeutic approach to autoimmunity and allergy.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anti-Bacterial Agents / pharmacology
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Cecum / microbiology
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Cells, Cultured
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Clostridium / growth & development
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Clostridium / immunology*
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Colitis / immunology
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Colitis / pathology
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Colitis / prevention & control
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Colon / immunology*
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Colon / metabolism
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Colon / microbiology*
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Feces / microbiology
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Forkhead Transcription Factors / metabolism
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Germ-Free Life
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Immunity, Innate
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Immunoglobulin E / biosynthesis
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Interleukin-10 / immunology
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Interleukin-10 / metabolism
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Intestinal Mucosa / immunology*
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Intestinal Mucosa / metabolism
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Intestine, Small / immunology
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Metagenome
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Mice
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Mice, Inbred A
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Mice, Inbred BALB C
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Receptors, Pattern Recognition / physiology
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Specific Pathogen-Free Organisms
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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
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Transforming Growth Factor beta / metabolism
Substances
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Anti-Bacterial Agents
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Forkhead Transcription Factors
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Foxp3 protein, mouse
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Receptors, Pattern Recognition
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Transforming Growth Factor beta
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Interleukin-10
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Immunoglobulin E