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

• Published in: Cell reports (Cambridge) Vol. 42; no. 2; p. 112074
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 28.02.2023
• Subjects: Animals; Gastrointestinal Microbiome; gut-lung axis; helminth infection; Immunity, Innate; Inflammation; innate lymphoid cells; Lung; Lymphocytes; maternal; Mice; Mice, Inbred C57BL; microbiota; neonatal; short-chain fatty acids; type 2 immunity; γδT cells; microbiota; CP: Immunology; gut-lung axis; helminth infection; CP: Microbiology; neonatal; innate lymphoid cells; short-chain fatty acids; γδT cells; type 2 immunity; maternal
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2023.112074

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. [Display omitted] •The offspring of γδ T cell-deficient dams display enhanced lung type 2 immunity•TCRδ−/− dams display differences in AMP levels and microbiota composition in the skin•Transfer of microbiota during birth and fostering regulates the first-breath reaction•SCFAs pentanoate and hexanoate suppress ILC2 functions and lung inflammation Papotto et al. show that the offspring of γδ T cell-deficient dams acquire perinatally a gut microbiota with decreased capacity of short-chain fatty acid (SCFA) production, leading to enhanced lung type 2 immune activation during steady state and infection. This regulatory neonatal gut-lung axis acts via the SCFAs pentanoate and hexanoate.