Lactobacillus reuteri induces gut intraepithelial CD4+CD8αα+ T cells

Luisa Cervantes-Barragan, Jiani N. Chai, Ma Diarey Tianero, Blanda Di Luccia, Philip P. Ahern, Joseph Merriman, Victor S. Cortez, Michael G. Caparon, Mohamed S. Abou Donia, Susan Gilfillan, Marina Cella, Jeffrey I. Gordon, Chyi Song Hsieh, Marco Colonna

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147 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)806-810
Number of pages5
JournalScience
Volume357
Issue number6353
DOIs
StatePublished - Aug 25 2017

All Science Journal Classification (ASJC) codes

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    Cervantes-Barragan, L., Chai, J. N., Tianero, M. D., Di Luccia, B., Ahern, P. P., Merriman, J., Cortez, V. S., Caparon, M. G., Abou Donia, M. S., Gilfillan, S., Cella, M., Gordon, J. I., Hsieh, C. S., & Colonna, M. (2017). Lactobacillus reuteri induces gut intraepithelial CD4+CD8αα+ T cells. Science, 357(6353), 806-810. https://doi.org/10.1126/science.aah5825