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Maternal γδ T Cells Shape Offspring Pulmonary Type-2 Immunity In A Microbiota-Dependent Manner

By Pedro H. Papotto, Bahtiyar Yilmaz, Gonçalo Pimenta, Sofia Mensurado, Carolina Cunha, Gina J. Fiala, Daniel Gomes da Costa, Natacha Gonçalves-Sousa, Brian H. K. Chan, Birte Blankenhaus, Tânia Carvalho, Andrew J. Macpherson, Judith E. Allen, Bruno Silva-Santos

Posted 14 Aug 2021
bioRxiv DOI: 10.1101/2021.08.13.456265

Immune system development is greatly influenced by vertically transferred cues. However, beyond antibody-producing B cells, little is known about the role of other cell subsets of the maternal immune system in regulating offspring immunity. We reasoned {gamma}{delta} T cells to be attractive candidates based on their tissue distribution pattern: abundant in the skin, mammary glands and female reproductive tract. Here we found that mice born from {gamma}{delta} T cell-deficient (TCR{delta}-/-) dams display, early after birth, a pulmonary milieu selectively enriched in type-2 cytokines such as IL-33, IL-4, IL-5, and IL-13, and type-2-polarized immune cells, when compared to the progeny of {gamma}{delta} T cell-sufficient dams. In addition, upon helminth infection, mice born from TCR{delta}-/- dams sustained an increased type-2 inflammatory response. Critically, this was independent of the genotype of the pups. Despite similar levels of circulating antibodies in mothers and progeny, the intestinal microbiota in the offspring of TCR{delta}-/- and TCR{delta}+/- dams harbored distinct bacterial communities acquired during birth and fostering. These differences were accompanied by changes in the intestinal short-chain fatty acids (SCFA) profile. Importantly, antibiotic treatment abrogated the differences observed in the pulmonary milieu, and exogenous SCFA supplementation suppressed first-breath- and infection-induced inflammation. In summary, maternal {gamma}{delta} T cells control the establishment of a neonatal gut-lung axis by conditioning the postnatal microbial colonization of the offspring and bacterial-derived metabolite availability; ultimately impacting on the development of pulmonary type-2 immunity in the offspring.

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