MAIT cell heterogeneity across paired human tissues reveals specialization of distinct regulatory and enhanced effector profiles.

Kammann T, Cai C, Sekine T, Mouchtaridi E, Boulouis C, Nilsén V, Ballesteros OR, Müller TR, Gao Y, Raineri EJM, Mily A, Adamo S, Constantz C, Niessl J, Weigel W, Kokkinou E, Stamper C, Marchalot A, Bassett J, Ferreira S, Rødahl I, Wild N, Brownlie D, Tibbitt C, Mak JYW, Fairlie DP, Leeansyah E, Michaelsson J, Marquardt N, Mjösberg J, Jorns C, Buggert M, Sandberg JK

Sci Immunol 9 (99) eadn2362 [2024-09-06; online 2024-09-06]

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.

Affinity Proteomics Stockholm [Service]

PubMed 39241054

DOI 10.1126/sciimmunol.adn2362

Crossref 10.1126/sciimmunol.adn2362