Immune Cell Function and Interaction
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Functional heterogeneity and tissue site adaptation in resident MAIT cells across human barrier tissues with distinct regulatory and effector signatures are demonstrated and highlight the phenotypic and functional specialization of human MAIT cells within specific tissue sites.
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Mucosal-associated invariant T (MAIT) cells are unconventional T cells that recognize microbial riboflavin pathway metabolites presented by evolutionarily conserved MR1 molecules. We explored the human MAIT cell compartment across organ donor-matched blood, barrier, and lymphoid tissues. MAIT cell population size was donor dependent with distinct tissue compartmentalization patterns and adaptations: Intestinal CD103+ resident MAIT cells presented an immunoregulatory CD39highCD27low profile, whereas MAIT cells expressing NCAM1/CD56 dominated in the liver and exhibited enhanced effector capacity with elevated response magnitude and polyfunctionality. Both intestinal CD39high and hepatic CD56+ adaptations accumulated with donor age. CD56+ MAIT cells displayed limited T cell receptor-repertoire breadth, elevated MR1 binding, and a transcriptional profile skewed toward innate activation pathways. Furthermore, CD56 was dynamically up-regulated to a persistent steady-state equilibrium after exposure to antigen or IL-7. In summary, we demonstrate functional heterogeneity and tissue site adaptation in resident MAIT cells across human barrier tissues with distinct regulatory and effector signatures.
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@article{Kammann2024MAIT,
title = {MAIT cell heterogeneity across paired human tissues reveals specialization of distinct regulatory and enhanced effector profiles},
author = {Tobias Kammann and Curtis Cai and Takuya Sekine and Elli Mouchtaridi and Caroline Boulouis and Vera Nilsén and Olga Rivera‐Ballesteros and Thomas Müller and Yu Gao and Elisa J. M. Raineri and Akhirunnesa Mily and Sarah Adamo and Christian M. Constantz and Julia Niessl and Whitney Weigel and Efthymia Kokkinou and Christopher Stamper and Anne Marchalot and John Bassett and Sabrina Antunes Ferreira and Inga Rødahl and Nicole Wild and Demi Brownlie and Christopher A. Tibbitt and Jeffrey Y. W. Mak and David P. Fairlie and Edwin Leeansyah and Jakob Michaëlsson and Nicole Marquardt and Jenny Mjösberg and Carl Jorns and Marcus Buggert and Johan K. Sandberg},
journal = {Science Immunology},
year = {2024},
doi = {10.1126/sciimmunol.adn2362},
url = {https://doi.org/10.1126/sciimmunol.adn2362}
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