CD4+CD8αα+ double-positive intraepithelial lymphocytes (DP IELs) serve regulatory roles in the small intestine. In Science, Cervantes-Barragan et al. show that the commensal Lactobacillus reuteri can induce the generation of DP IELs in C57BL/6 mice. L. reuteri is found in mice from Charles River Laboratories but not in those from Jackson Laboratories. L. reuteri metabolizes tryptophan to indole-3-lactic acid, which is a ligand for the transcription factor Ahr. The generation of DP IELs requires Ahr to act in conjunction with cytokine TGF-β signaling to downregulate expression of the transcriptional regulator ThPOK in CD4+ T cells, which derepresses expression of Cd8a. The presence of this lactobacillus plus a tryptophan-rich diet might therefore be beneficial in patients with irritable bowel disease.

Science 357, 806–810 (2017)