MAIT cell heterogeneity across paired human tissues reveals specialization of distinct regulatory and enhanced effector profiles
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<sup>+</sup> resident MAIT cells presented an immunoregulatory CD39<sup>high</sup>CD27<sup>low</sup> profile, whereas MAIT cells expressing NCAM1/CD56 dominated in the liver and exhibited enhanced effector capacity with elevated response magnitude and polyfunctionality. Both intestinal CD39<sup>high</sup> and hepatic CD56<sup>+</sup> adaptations accumulated with donor age. CD56<sup>+</sup> 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.
Authors
- Nicole Marquardt (ORCID: https://orcid.org/0000-0003-3186-4752)
- Jakob Michaëlsson (ORCID: https://orcid.org/0000-0001-6948-7281)
- Carl Jorns (ORCID: https://orcid.org/0000-0001-7727-8113)
- John Bassett (ORCID: https://orcid.org/0000-0002-9509-0752)
- Efthymia Kokkinou (ORCID: https://orcid.org/0000-0001-9248-4740)
- Curtis Cai (ORCID: https://orcid.org/0000-0002-3490-4361)
- Akhirunnesa Mily (ORCID: https://orcid.org/0000-0003-3136-9284)
- Demi Brownlie (ORCID: https://orcid.org/0000-0001-5932-6425)
- Vera Nilsén
- Julia Niessl (ORCID: https://orcid.org/0000-0001-8852-1924)
- Nicole Wild (ORCID: https://orcid.org/0000-0002-4009-473X)
- Caroline Boulouis (ORCID: https://orcid.org/0000-0003-0562-5395)
- Jeffrey Y. W. Mak (ORCID: https://orcid.org/0000-0002-8011-4539)
- Sabrina Antunes Ferreira (ORCID: https://orcid.org/0000-0003-0931-2150)
- Christopher T. Stamper (ORCID: https://orcid.org/0000-0002-5568-8880)
- Sarah Adamo (ORCID: https://orcid.org/0000-0002-6161-3156)
- Yu Gao (ORCID: https://orcid.org/0000-0002-4615-3614)
- Anne Marchalot (ORCID: https://orcid.org/0000-0002-3042-8206)
- Christopher A. Tibbitt (ORCID: https://orcid.org/0000-0002-7730-7700)
- Inga Rødahl (ORCID: https://orcid.org/0000-0001-7517-9023)
- David P. Fairlie (ORCID: https://orcid.org/0000-0002-7856-8566)
- Marcus Buggert (ORCID: https://orcid.org/0000-0003-0633-1719)
- Elisa J. M. Raineri (ORCID: https://orcid.org/0000-0002-5468-276X)
- Tobias Kammann (ORCID: https://orcid.org/0000-0002-8433-036X)
- Johan K. Sandberg (ORCID: https://orcid.org/0000-0002-6275-0750)
- Christian M. Constantz
- Elli Mouchtaridi
- Thomas Müller (ORCID: https://orcid.org/0000-0001-5331-5522)
- Takuya Sekine (ORCID: https://orcid.org/0000-0001-7649-0593)
- Jenny Mjösberg (ORCID: https://orcid.org/0000-0002-1119-0976)
- Whitney Weigel (ORCID: https://orcid.org/0000-0003-2218-4026)
- Olga Rivera‐Ballesteros (ORCID: https://orcid.org/0000-0001-6949-4270)
- Edwin Leeansyah (ORCID: https://orcid.org/0000-0003-0505-4967)
Institutions
- Karolinska University Hospital (SE)
- Australian Research Council (AU)
- Karolinska Institutet (SE)
- Tsinghua–Berkeley Shenzhen Institute (CN)
- ARC Centre of Excellence for Innovations in Peptide and Protein Science (AU)
- Tsinghua University (CN)
Publication Details
- Journal
- Science Immunology
- Published
- 2024-09-06
- DOI
- https://doi.org/10.1126/sciimmunol.adn2362
- Citations
- 27
- Primary Topic
- Immune Cell Function and Interaction
- Type
- article
- Field-Weighted Citation Impact
- 6.49
Funders
- Stiftelsen Tornspiran
- Monash University
- Cancerfonden
- Svenska Sällskapet för Medicinsk Forskning
- Hjärt-Lungfonden
- Karolinska Institutet
- Knut och Alice Wallenbergs Stiftelse
- Stockholms Läns Landsting
- Vetenskapsrådet
- Science for Life Laboratory
- Science, Technology and Innovation Commission of Shenzhen Municipality
- National Institutes of Health
- National Health and Medical Research Council
- Uppsala Multidisciplinary Center for Advanced Computational Science
- Center for Innovative Medicine
- Tsinghua Shenzhen International Graduate School