Mucosal-associated invariant T cells restrict reactive oxidative damage and preserve meningeal barrier integrity and cognitive function
Open accessAbstract
Increasing evidence indicates close interaction between immune cells and the brain, revising the traditional view of the immune privilege of the brain. However, the specific mechanisms by which immune cells promote normal neural function are not entirely understood. Mucosal-associated invariant T cells (MAIT cells) are a unique type of innate-like T cell with molecular and functional properties that remain to be better characterized. In the present study, we report that MAIT cells are present in the meninges and express high levels of antioxidant molecules. MAIT cell deficiency in mice results in the accumulation of reactive oxidative species in the meninges, leading to reduced expression of junctional protein and meningeal barrier leakage. The presence of MAIT cells restricts neuroinflammation in the brain and preserves learning and memory. Together, our work reveals a new functional role for MAIT cells in the meninges and suggests that meningeal immune cells can help maintain normal neural function by preserving meningeal barrier homeostasis and integrity.
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MAIT cells are responsible for preserving meningeal homeostasis by expressing antioxidant molecules, as evidenced by increased oxidative damage and impaired meningeal barrier integrity in MAIT cell-deficient Mr1-/- mice compared to their age-matched Mr1+/+ counterparts.
“MAIT cells are responsible for preserving meningeal homeostasis by expressing antioxidant molecules, as evidenced by increased oxidative damage and impaired meningeal barrier integrity in MAIT cell-deficient Mr1–/– mice compared to their age-matched Mr1+/+ counterparts.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [688]
Mr1-/- mice exhibited extensive microgliosis in the cortex and hippocampus, along with impaired cognitive function.
“Mr1–/– mice exhibited extensive microgliosis in the cortex and hippocampus, along with impaired cognitive function.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [688]
These defects were prevented by the adoptive transfer of MAIT cells from WT mice, supporting the protective functions of MAIT cells on the meningeal barrier.
“these defects were prevented by the adoptive transfer of MAIT cells from WT mice, supporting the protective functions of MAIT cells on the meningeal barrier.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [688]
MAIT cells are a key mediator of the gut-meningeal axis.
“A key mediator of the gut–meningeal axis is the mucosal-associated invariant T (MAIT) cells.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [688]
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- Authors
- Zhang, Y., Bailey, J. T., Xu, E., Singh, K., Lavaert, M., Link, V. M., D’Souza, S., Hafiz, A., Cao, J., Cao, G., Sant’Angelo, D. B., Sun, W., Belkaid, Y., Bhandoola, A., McGavern, D. B., & Yang, Q.
- Affiliations
- Rutgers, The State University of New Jersey (US)
- Albany Medical College (US)
- National Institutes of Health (US)
- Rutgers Cancer Institute (US)
- Corresponding author
- Yang, Qi
- ORCID
- Venue
- Nature Immunology
- Published
- 2022-11-21
- Volume
- 23
- Issue
- 12
- Pages
- 1714-1725
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- PMC
- PMC10202031
- OpenAlex
- W4309655079
- Cited by
- 91
- References
- 47
- Citations by year
- 2026: 17 · 2025: 26 · 2024: 24 · 2023: 20 · 2022: 4
- FWCI
- 6.49
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Health & Human Services | National Institutes of Health (R01HL137813, R01AG057782, R01HL155021)
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIH Intramural Research Program)
- U.S. Department of Health & Human Services | NIH | National Cancer Institute (NIH intramural research program)
- U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NIH intramural research program)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- mucosal-associated invariant T cells, meninges, reactive oxygen species, antioxidants, neuroinflammation, learning and memory, innate-like T cells, junctional proteins
- MeSH terms
- Mucosal-Associated Invariant T Cells, Animals, Brain, Cognition, Meninges, Oxidative Stress, Mice
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