Maternal ?? T cells shape offspring pulmonary type 2 immunity in a microbiota-dependent manner

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 y8 T cell-deficient (TCR(1-/-) 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 y8 T cell-sufficient dams. Upon helminth infection, mice born from TCR(1-/- dams sustain an increased type 2 inflammatory response. This is independent of the genotype of the pups. Instead, the offspring of TCR(1-/- 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. Im-portantly, 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 y8 T cell-microbiota-SCFA axis regulating neonatal lung immunity.