Papotto, Pedro H; Yilmaz, Bahtiyar; Pimenta, Gonçalo; Mensurado, Sofia; Cunha, Carolina; Fiala, Gina J; Gomes da Costa, Daniel; Gonçalves-Sousa, Natacha; Chan, Brian H K; Blankenhaus, Birte; Domingues, Rita G; Carvalho, Tânia; Hepworth, Matthew R; Macpherson, Andrew J; Allen, Judith E; Silva-Santos, Bruno (2023). Maternal γδ T cells shape offspring pulmonary type 2 immunity in a microbiota-dependent manner. Cell reports, 42(2), p. 112074. Cell Press 10.1016/j.celrep.2023.112074
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1-s2.0-S2211124723000852-main.pdf - Published Version Available under License Creative Commons: Attribution (CC-BY). Download (5MB) | Preview |
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.
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