1. Lactobacillus reuteri induces gut intraepithelial CD4 + CD8αα + T cells.
- Author
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Cervantes-Barragan L, Chai JN, Tianero MD, Di Luccia B, Ahern PP, Merriman J, Cortez VS, Caparon MG, Donia MS, Gilfillan S, Cella M, Gordon JI, Hsieh CS, and Colonna M
- Subjects
- Animals, Basic Helix-Loop-Helix Transcription Factors metabolism, Down-Regulation, Germ-Free Life, Indoles metabolism, Intestinal Mucosa immunology, Intestinal Mucosa microbiology, Mice, Mice, Inbred C57BL, Receptors, Aryl Hydrocarbon metabolism, Transcription Factors metabolism, Tryptophan metabolism, CD4-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes immunology, Gastrointestinal Microbiome immunology, Intestine, Small immunology, Intestine, Small microbiology, Limosilactobacillus reuteri immunology
- Abstract
The small intestine contains CD4
+ CD8αα+ double-positive intraepithelial lymphocytes (DP IELs), which originate from intestinal CD4+ T cells through down-regulation of the transcription factor Thpok and have regulatory functions. DP IELs are absent in germ-free mice, which suggests that their differentiation depends on microbial factors. We found that DP IEL numbers in mice varied in different vivaria, correlating with the presence of Lactobacillus reuteri This species induced DP IELs in germ-free mice and conventionally-raised mice lacking these cells. L. reuteri did not shape the DP-IEL-TCR (TCR, T cell receptor) repertoire but generated indole derivatives of tryptophan that activated the aryl-hydrocarbon receptor in CD4+ T cells, allowing Thpok down-regulation and differentiation into DP IELs. Thus, L. reuteri , together with a tryptophan-rich diet, can reprogram intraepithelial CD4+ T cells into immunoregulatory T cells., (Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)- Published
- 2017
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