Maternal γδ T cells shape offspring pulmonary type 2 immunity in a microbiota-dependent manner
Pedro H. Papotto, Bahtiyar Yılmaz, Gonçalo Pimenta, Sofia Mensurado, Carolina Cunha, Gina J. Fiala, D.G. Costa, Natacha Gonçalves‐Sousa, Brian H. K. Chan, Birte Blankenhaus, Rita G. Domingues, Tânia Carvalho, Matthew R. Hepworth, Andrew J. Macpherson, Judith E. Allen, Bruno Silva‐Santos
Abstract
Immune development is profoundly influenced by vertically transferred cues. However, little is known about how maternal innate-like lymphocytes regulate offspring immunity. Here, we show that mice born from γδ T cell-deficient ( TCRδ −/− ) dams display an increase in first-breath-induced inflammation, with a pulmonary milieu selectively enriched in type 2 cytokines and type 2-polarized immune cells, when compared with the progeny of γδ T cell-sufficient dams. Upon helminth infection, mice born from TCRδ −/− dams sustain an increased type 2 inflammatory response. This is independent of the genotype of the pups. Instead, the offspring of TCRδ −/− dams harbors a distinct intestinal microbiota, acquired during birth and fostering, and decreased levels of intestinal short-chain fatty acids (SCFAs), such as pentanoate and hexanoate. Importantly, exogenous SCFA supplementation inhibits type 2 innate lymphoid cell function and suppresses first-breath- and infection-induced inflammation. Taken together, our findings unravel a maternal γδ T cell-microbiota-SCFA axis regulating neonatal lung immunity.