Lactobacillus reuteri induces gut intraepithelial CD4+CD8αα+ T cells

By L. Cervantes-Barragan, Jiani N. Chai, M. Tianero, B. Di Luccia, Philip P. Ahern, Joseph A. Merriman, V. Cortez, M. Caparon, Mohamed S. Donia, S. Gilfillan and 4 more. Science, 2017

764 citations recorded by the source corpus.

Tolerogenic T cells need probiotics CD4+CD8αα+ double-positive intraepithelial lymphocytes (DP IELs) are a recently discovered class of intestinal T cells believed to take part in a variety of immune responses, including oral tolerance. These cells are absent in germ-free mice, but the mechanisms driving their development are unclear. Cervantes-Barragan et al. found that a particular species of probiotic bacteria, Lactobacillus reuteri, induces DP IELs. This does not occur by stimulating the immune system directly. Instead, L. reuteri generates a specific derivative of dietary tryptophan that promotes differentiation of DP IEL precursors. These findings underscore the delicate interplay between benign bacteria, diet, and gut health. Science, this issue p. 806 Lactobacillus reuteri induces a specific type of gut intraepithelial T cell via tryptophan catabolites that activate the aryl hydrocarbon receptor. 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.

Subfields: Food Science, Molecular Biology, Surgery

View Paper: https://www.semanticscholar.org/paper/2049330d458d13ece88cc1059e89b6d02ffa656f

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In Molecular Biology

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Citations in the corpus

• Role of Lactobacillus reuteri in Human Health and Diseases (2018, background): “In addition, the derivatives of tryptophan generated by L. reuteri can induce the development of regulatory CD4+CD8αα+ double-positive intraepithelial lymphocytes in an AhR-dependent manner (Cervantes-Barragan et al., 2017).”
• The gut microbiome: Relationships with disease and opportunities for therapy (2018, background): “, 2015), lack regulatory gut CD4+CD8αα+ double-positive intra-epithelial lymphocytes (Cervantes-Barragan et al., 2017), have compromised innate lymphoid cell function (Hepworth et al.”
• Anti-Inflammatory and Immunomodulatory Effects of Probiotics in Gut Inflammation: A Door to the Body (2021, background): “reuteri 100-23 associated with a diet enriched in tryptophan was able to repolarize gut intraepithelial CD4+ T cells- into Treg cells enhancing immunotolerance (109).”
• Regulation of the immune response by the aryl hydrocarbon receptor (2018, background): “Additionally, AhR activation by microbial metabolites also controls the generation of DP IELs, another important population in the control of intestinal immunity (Cervantes-Barragan et al., 2017).”
• Gut Microbiota Regulation of Tryptophan Metabolism in Health and Disease. (2018, background): “Similarly, Lactobacillus reuteri, through the production of the AhR agonist indole-3-lactic acid, is able to reprogram intraepithelial CD4+ T cells into immunoregulatory CD4+CD8aa+ T cells (Cervantes-Barragan et al., 2017).”