Protective effect of TCR-mediated MAIT cell activation during experimental autoimmune encephalomyelitis

Mark Walkenhorst, Jana K. Sonner, Nina Meurs, Jan Broder Engler, Simone Bauer, Ingo Winschel, Marcel S. Woo, Lukas Raich, Iris Winkler, Vanessa Vieira, Lisa Unger, Gabriela Salinas, Olivier Lantz, Manuel A. Friese () and Anne Willing ()
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Mark Walkenhorst: University Medical Center Hamburg-Eppendorf
Jana K. Sonner: University Medical Center Hamburg-Eppendorf
Nina Meurs: University Medical Center Hamburg-Eppendorf
Jan Broder Engler: University Medical Center Hamburg-Eppendorf
Simone Bauer: University Medical Center Hamburg-Eppendorf
Ingo Winschel: University Medical Center Hamburg-Eppendorf
Marcel S. Woo: University Medical Center Hamburg-Eppendorf
Lukas Raich: University Medical Center Hamburg-Eppendorf
Iris Winkler: University Medical Center Hamburg-Eppendorf
Vanessa Vieira: University Medical Center Hamburg-Eppendorf
Lisa Unger: University Medical Center Hamburg-Eppendorf
Gabriela Salinas: University Medical Center Göttingen
Olivier Lantz: Institut Curie
Manuel A. Friese: University Medical Center Hamburg-Eppendorf
Anne Willing: University Medical Center Hamburg-Eppendorf

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract Mucosal-associated invariant T (MAIT) cells express semi-invariant T cell receptors (TCR) for recognizing bacterial and yeast antigens derived from riboflavin metabolites presented on the non-polymorphic MHC class I-related protein 1 (MR1). Neuroinflammation in multiple sclerosis (MS) is likely initiated by autoreactive T cells and perpetuated by infiltration of additional immune cells, but the precise role of MAIT cells in MS pathogenesis remains unknown. Here, we use experimental autoimmune encephalomyelitis (EAE), a mouse model of MS, and find an accumulation of MAIT cells in the inflamed central nervous system (CNS) enriched for MAIT17 (RORγt+) and MAIT1/17 (T-bet+RORγt+) subsets with inflammatory and protective features. Results from transcriptome profiling and Nur77GFP reporter mice show that these CNS MAIT cells are activated via cytokines and TCR. Blocking TCR activation with an anti-MR1 antibody exacerbates EAE, whereas enhancing TCR activation with the cognate antigen, 5-(2-oxopropylideneamino)−6-D-ribitylaminouracil, ameliorates EAE severity, potentially via the induction of amphiregulin (AREG). In summary, our findings suggest that TCR-mediated MAIT cell activation is protective in CNS inflammation, likely involving an induction of AREG.

Date: 2024
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DOI: 10.1038/s41467-024-53657-9

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