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Lactobacillus reuteri induces gut intraepithelial CD4+CD8αα+ T cells

Luisa Cervantes-Barragan1, Jiani N Chai1,2, Ma Diarey Tianero3

  • 1Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.

Science (New York, N.Y.)
|August 5, 2017
PubMed

Insights

Lactobacillus reuteri, a gut microbe, promotes the development of regulatory T cells in the small intestine. This bacterium reprograms CD4+ T cells into CD4+CD8αα+ double-positive intraepithelial lymphocytes (DP IELs) via tryptophan metabolites.

Area of Science:

  • Immunology
  • Microbiology
  • Gastroenterology

Background:

  • CD4+CD8αα+ double-positive intraepithelial lymphocytes (DP IELs) are regulatory T cells in the small intestine.
  • DP IELs originate from CD4+ T cells via Thpok down-regulation and are absent in germ-free mice, suggesting microbial influence.

Purpose of the Study:

  • To investigate the microbial factors responsible for DP IEL differentiation.
  • To elucidate the mechanism by which microbes induce DP IELs.

Main Methods:

  • Comparative analysis of DP IEL numbers in mice from different vivaria.
  • Induction of DP IELs in germ-free and conventionally-raised mice using *Lactobacillus reuteri*.
  • Analysis of TCR repertoire and metabolite production by *L. reuteri*.

Main Results:

  • DP IEL numbers correlated with the presence of *Lactobacillus reuteri* across different vivaria.
  • *L. reuteri* induced DP IELs in mice lacking these cells.
  • *L. reuteri* produced indole derivatives of tryptophan, activating the aryl-hydrocarbon receptor in CD4+ T cells, leading to Thpok down-regulation and DP IEL differentiation.

Conclusions:

  • *Lactobacillus reuteri* is a key microbial factor driving DP IEL differentiation.
  • Microbial metabolites, specifically tryptophan derivatives, reprogram CD4+ T cells into immunoregulatory DP IELs.
  • A tryptophan-rich diet combined with *L. reuteri* can modulate intraepithelial T cell populations.

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