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Induction of colonic regulatory T cells by indigenous Clostridium species.

Science (New York, N.Y.)

metabolism, Transforming Growth Factor beta, immunology, T-Lymphocytes, Regulatory, T-Lymphocytes, Helper-Inducer, Specific Pathogen-Free Organisms, physiology, Receptors, Pattern Recognition, Mice, Inbred BALB C, Mice, Inbred A, Mice, Metagenome, Intestine, Small, Intestinal Mucosa, Interleukin-10, biosynthesis, Immunoglobulin E, Immunity, Innate, Germ-Free Life, Forkhead Transcription Factors, microbiology, Feces, Colon, prevention & control, pathology, Colitis, growth & development, Clostridium, Cells, Cultured, Cecum, pharmacology, Anti-Bacterial Agents, Animals

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      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.

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      Journal
      10.1126/science.1198469
      3969237
      21205640

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