The role of the microbiota in the development and function of γδ T cells—a T cell subset characterized by a T cell receptor composed of one γ-chain and one δ-chain—has been investigated in multiple organs in mice and humans. Interactions between the microbiota and γδ T cells affect both tissue homeostasis and disease pathologies. Notably, microbiota-induced interleukin-17 (IL-17)-producing-γδ T cells can mediate a range of immunological processes, from metabolic disorders to neuroinflammation via the gut–brain axis. However, the bidirectional interactions between γδ T cells and the microbiota have not been fully determined. In this Perspective, we dissect the roles of microbiota in modulating γδ T cell development and function, and evaluate the evidence for γδ T cell selection of commensal communities. We also discuss the potential implications of these cells in health and disease and the major open questions and research avenues in the field.
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We thank J. C. Ribot for insightful discussions on this topic. Figures were created with BioRender.com. Our work is supported by European Molecular Biology Organization (LTF 191-2019) to P.H.P., Swiss National Foundation (SNF) Ambizione Grant PZ00P3_185880 and Novartis Foundation for Medical-Biological Research (no. 19A013) to B.Y., and ‘la Caixa’ Foundation (ID 100010434, LCF/PR/HR19/52160011) to B.S.-S.
The authors declare no competing interests.
Peer review information Nature Microbiology thanks Dennis Kasper and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.
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Papotto, P.H., Yilmaz, B. & Silva-Santos, B. Crosstalk between γδ T cells and the microbiota. Nat Microbiol 6, 1110–1117 (2021). https://doi.org/10.1038/s41564-021-00948-2