Maternal γδ T cells shape offspring pulmonary type 2 immunity in a microbiota-dependent manner
Year: 2023
Type: article
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.
Source: Cell Reports
Authors: Pedro H. Papotto, Bahtiyar Yilmaz, Gonçalo Pimenta, Sofia Mensurado, Carolina Cunha, Gina J. Fiala, Daniel Gomes da 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
Language: English
Topic: IL-33, ST2, and ILC Pathways
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,460
Funders: European Molecular Biology Organization, Novartis Foundation, University of Bern, Wellcome Trust, Royal Society, University of Manchester, European Commission, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Novartis Stiftung für Medizinisch-Biologische Forschung, Medical Research Council, Biotechnology and Biological Sciences Research Council, Fundação para a Ciência e a Tecnologia
Awards: G1491354068, Regenerative medicine: instrumentation for flow cytometry and cell printing, Evolutionary dynamics of bacteria in the intestines of IBD patients, Innate immune regulation of pathologic CD4+ T cell responses in inflammatory disease., Inter-tissue communication during nematode infections: role of dermal γδ17 T cells, Amino acid availability acts as a critical environmental rheostat of mucosal ILC2 responses, G3549705213, Innate immune regulation of pathologic CD4+ T cell responses in inflammatory disease., G3909163727, Tracking γδ T cell development and TCRγδ proximal signalling, Chitinase-like proteins: Host protection through molecular multi-tasking., G414171495, Regulação dos linfócitos T gama-delta no microambiente tumoral e sua manipulação para imunoterapia de cancros sólidos, G5467012935, Chitinase-like proteins: Host protection through molecular multi-tasking., Enhanced integration of primary and secondary health systems and patient empowerment through improved continuity of patient care and clinical handover, G6071825221, G8376925532
OpenAlex ID: W4320487454