Maternal administration of probiotics augments IL17-committed ?d T cells in the newborn lung

The early-life period is increasingly being recognized as a window of opportunity to shape immunity where microbiota and related probiotics have an important impact. Innate ?d T cells are the first T cells generated in utero populating epithelial tissues such as the lung contributing to tissue protection through, for example, IL17 production. Here, we studied the influence of maternal microbiota and probiotic supplementation during pregnancy on innate ?d T cells in the lung and thymus of newborn mice. Detailed time-kinetic experiments showed that at birth the murine lung T cell population was specifically dominated by IL17-committed ?d T cells expressing an invariant V?6Vd1 TCR. Single-cell-RNA-sequencing showed that the biased IL17-commitment of perinatal lung ?dT cells is highly conserved between mice and humans. While maternal microbiota depletion with antibiotics tended to decrease the frequency of the lung V?6 T cells of the offspring at birth, the maternal administration of Lacticaseibacillus rhamnosus(L.rhm.), but not of Bifidobacterium animalis subsp.lactis(B.lac.), increased significantly their frequency resulting in the augmentation of the IL17-commitment of the mouse lung T cell compartment. Altogether, our data indicate that the maternal microbiota contributes to the shaping of IL17-committed ?dT cells in the lungs of newborns and that maternal administration of specific probiotic strains can enhance this process. Overall design: ?dT cells were sorted from fetal lung samples, followed by 5'-RNA single cell transcriptome and TCR sequening (10x genomics).