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A three-stage intrathymic development pathway for the mucosal-associated invariant T cell lineage
Abstract
Mucosal-associated invariant T cells (MAIT cells) detect microbial vitamin B2 derivatives presented by the antigen-presenting molecule MR1. Here we defined three developmental stages and checkpoints for the MAIT cell lineage in humans and mice. Stage 1 and stage 2 MAIT cells predominated in thymus, while stage 3 cells progressively increased in abundance extrathymically. Transition through each checkpoint was regulated by MR1, whereas the final checkpoint that generated mature functional MAIT cells was controlled by multiple factors, including the transcription factor PLZF and microbial colonization. Furthermore, stage 3 MAIT cell populations were expanded in mice deficient in the antigen-presenting molecule CD1d, suggestive of a niche shared by MAIT cells and natural killer T cells (NKT cells). Accordingly, this study maps the developmental pathway and checkpoints that control the generation of functional MAIT cells.
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“The development and maturation of MAIT cells are dependent on microbiota, as demonstrated by reduced numbers of MAIT cells in GF mice, which can be restored through microbial colonization.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [691]
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“A comparison of mice housed in conventional specific-pathogen-free (SPF) conditions to germ-free (GF) animals confirmed previous observations that the microbiota is necessary for the presence of MAIT cells in the thymus, spleen, and gut (17, 18), and extended this requirement for MAIT cells in the skin, lungs, and liver (Fig. 1B).”
From MAIT cells are imprinted by the microbiota in early life and promote tissue repair (2019) · cites this paper as [18]
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Gu, S., Zhang, P., Zhang, C., Tang, T.-X., Chang, T., Dong, L., Gao, W., & Tang, Z. (2025) · Journal of Inflammation Research · doi:10.2147/jir.s545532 · Cited by 3
CD2 and its ligands are involved in development and activation of MAIT cells
Zhu, K., Dou, J., Li, B., Qian, J., Zhong, M., Tang, Z.-H., Lü, Y., & Veillette, A. (2025) · The Journal of Experimental Medicine · doi:10.1084/jem.20250431 · Cited by 4
Oketade, N., Chengalroyen, M. D., Kain, D. C., Lewinsohn, D. M., & Dobos, K. M. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1656167 · Cited by 3
Dual Roles of MAIT Cells in the Tumor Microenvironment: Implications for Cancer Immunity and Therapy
Choi, J., & Lee, Y. J. (2026) · Immune Network · doi:10.4110/in.2026.26.e8 · Cited by 3
Functional spectrum of γδ T cells in perinatal infectious diseases
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Konecny, A., Shows, D. M., & Lord, J. D. (2023) · PLoS ONE · doi:10.1371/journal.pone.0285918 · Cited by 3
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Mucosal‐Associated Invariant T Cells in Rheumatic Diseases
Lesturgie-Talarek, M., Gonzalez, V., Beaudoin, L., Sénot, N., Miceli‐Richard, C., Allanore, Y., Lehuen, A., & Avouac, J. (2025) · Arthritis & Rheumatology · doi:10.1002/art.43242 · Cited by 3
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Self-citationMAIT cells drive chronic inflammation in a genetically diverse murine model of spontaneous colitisPreprint
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Self-citationAntibiotic use in early life subsequently impairs MAIT cell-mediated immunityPreprint
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Antibiotic use in early life impairs MAIT cell–mediated immunity in adulthood
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Metadata
- Authors
- Koay, H.-F., Gherardin, N. A., Enders, A., Loh, L., Mackay, L. K., Almeida, C. F., Russ, B. E., Nold-Petry, C. A., Nold, M. F., Bedoui, S., Chen, Z., Corbett, A. J., Eckle, S. B. G., Meehan, B., d'Udekem, Y., Konstantinov, I. E., Lappas, M., Liu, L., Goodnow, C. C., Fairlie, D. P., Rossjohn, J., Chong, M. M., Kedzierska, K., Berzins, S. P., Belz, G. T., McCluskey, J., Uldrich, A. P., Godfrey, D. I., & Pellicci, D. G.
- Affiliations
- The University of Melbourne (AU)
- Hudson Institute of Medical Research (AU)
- Royal Children's Hospital (AU)
- The University of Queensland (AU)
- Monash University (AU)
- St Vincents Institute of Medical Research (AU)
- Federation University (AU)
- Corresponding author
- Godfrey, Dale I
- Pellicci, Daniel G
- ORCID
- Koay, Hui-Fern
- Gherardin, Nicholas A
- Enders, Anselm
- Loh, Liyen
- Mackay, Laura K
- Almeida, Catarina F
- Russ, Brendan E
- Nold, Marcel F
- Bedoui, Sammy
- Chen, Zhenjun
- Corbett, Alexandra J
- Eckle, Sidonia B G
- Meehan, Bronwyn
- Konstantinov, Igor E
- Lappas, Martha
- Liu, Ligong
- Goodnow, Chris C
- Fairlie, David P
- Rossjohn, Jamie
- Chong, Mark M
- Kedzierska, Katherine
- Berzins, Stuart P
- Belz, Gabrielle T
- McCluskey, James
- Uldrich, Adam P
- Godfrey, Dale I
- Pellicci, Daniel G
- Venue
- Nature Immunology
- Published
- 2016-09-26
- Volume
- 17
- Issue
- 11
- Pages
- 1300-1311
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W2526319073
- Cited by
- 377
- References
- 44
- Citations by year
- 2026: 26 · 2025: 36 · 2024: 36 · 2023: 36 · 2022: 44 · 2021: 40 · 2020: 52 · 2019: 40 · 2018: 39 · 2017: 25 · 2016: 3
- FWCI
- 21.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
- ANU Open Research (Australian National University) (submittedVersion)
- FedUni ResearchOnline (Federation University Australia) (submittedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Minerva Access (University of Melbourne) (submittedVersion)
- Funders
- National Heart Foundation of Australia
- Medical Research Council
- Australian Research Council (FT140100278, LE110100106)
- National Health and Medical Research Council (1054431, 1047025, 1013667, 1035858, 1106004, 1027369, CE140100011, 1023294, 1020770, 1083942, 1016629)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Keywords
- mucosal-associated invariant T cells, thymus development, MR1, PLZF, microbial colonization, CD1d, NKT cells, developmental checkpoints
- MeSH terms
- Mucosal-Associated Invariant T Cells, Animals, Cell Differentiation, Gene Expression Regulation, Humans, Male, Thymus Gland, Biomarkers, Immunophenotyping, Mice, Knockout, Gene Expression Profiling, MicroRNAs, Mice, Lymphoid Progenitor Cells, Antigens, CD1d
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