| Autor: |
Chandra, Shilpi, Ascui, Gabriel, Riffelmacher, Thomas, Chawla, Ashu, Ramírez-Suástegui, Ciro, Castelan, Viankail C., Seumois, Gregory, Simon, Hayley, Murray, Mallory P., Seo, Goo-Young, Premlal, Ashmitaa L. R., Schmiedel, Benjamin, Verstichel, Greet, Li, Yingcong, Lin, Chia-Hao, Greenbaum, Jason, Lamberti, John, Murthy, Raghav, Nigro, John, Cheroutre, Hilde |
| Předmět: |
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| Zdroj: |
Science Immunology; 2023, Vol. 8 Issue 89, p1-19, 19p |
| Abstrakt: |
Mucosal-associated invariant T (MAIT) cells are a subset of T lymphocytes that respond to microbial metabolites. We defined MAIT cell populations in different organs and characterized the developmental pathway of mouse and human MAIT cells in the thymus using single-cell RNA sequencing and phenotypic and metabolic analyses. We showed that the predominant mouse subset, which produced IL-17 (MAIT17), and the subset that produced IFN-γ (MAIT1) had not only greatly different transcriptomes but also different metabolic states. MAIT17 cells in different organs exhibited increased lipid uptake, lipid storage, and mitochondrial potential compared with MAIT1 cells. All these properties were similar in the thymus and likely acquired there. Human MAIT cells in lung and blood were more homogeneous but still differed between tissues. Human MAIT cells had increased fatty acid uptake and lipid storage in blood and lung, similar to human CD8 T resident memory cells, but unlike mouse MAIT17 cells, they lacked increased mitochondrial potential. Although mouse and human MAIT cell transcriptomes showed similarities for immature cells in the thymus, they diverged more strikingly in the periphery. Analysis of pet store mice demonstrated decreased lung MAIT17 cells in these so-called "dirty" mice, indicative of an environmental influence on MAIT cell subsets and function. Editor's summary: Mucosal-associated invariant T (MAIT) cells are a subset of T cells that sense microbial metabolites. Chandra et al. analyzed MAIT cells in mice and humans to better understand how the local environment influences MAIT cell development and function. They used single-cell RNA sequencing and phenotypic and metabolic analyses and observed that MAIT cell transcriptional and metabolic programs originated in the thymus but was also influenced by local tissue environment. IL-17–producing MAIT cells (MAIT17) were dominant in murine lung, and IFN-γ–producing MAIT1 cells were more frequent in the liver. "Dirty" pet store mice had fewer lung MAIT17 cells compared with lab strains, indicating influence of external environment. Human MAIT cells showed less heterogeneity than murine counterparts, and their properties differed more strikingly in the periphery. These findings confirm that the environment influences MAIT cell development and function. —Christiana Fogg [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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