Papotto, Pedro H.Yilmaz, BahtiyarPimenta, GonçaloMensurado, SofiaCunha, CarolinaFiala, GinaGomes Da Costa, DanielGonçalves-Sousa, NatachaChan, Brian H. K.Blankenhaus, BirteDomingues, Rita G.Carvalho, TâniaHepworth, Matthew R.Macpherson, Andrew J.Allen, Judith E.Silva-Santos, Bruno2024-07-252024-07-252023Cell Rep. 2023 Feb 28;42(2):1120742639-1856http://hdl.handle.net/10451/65467© 2023 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).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.engImmunologyMicrobiologyGut-lung axisHelminth infectionInnate lymphoid cellsMaternalMicrobiotaNeonatalShort-chain fatty acidsType 2 immunityγδT cellsjournal article10.1016/j.celrep.2023.1120742211-1247