The MR1/MAIT cell axis has limited effects on the start of tau pathology in a mouse model of tauopathy.

Immunity impacts all aspects of Alzheimer's disease (AD) pathology. Previously, we found improved pathology and cognition in the amyloid-focused 5XFAD mouse model deficient in the innate immune cell axis consisting of the innate-like mucosal-associated invariant T (MAIT) cells and the MHC class I-like antigen-presenting molecule they recognize, MR1. However, little is known about how a lack of the MR1/MAIT cell axis impacts cognition and whether an increased abundance of MAIT cells impacts pathology and cognition in the tau-focused PS19 mouse model. We crossed PS19 mice onto an MR1 KO background, resulting in a lack of both MR1 and MAIT cells, and alternatively, onto MAITCAST mice, that have ∼7× more MAIT cells. Using immunofluorescent microscopy, flow cytometry, and cognitive tests including Barnes maze and Novel Object Recognition, we analyzed the impact of MAIT cell numbers on tau pathology. Although an elevation in MAIT cell frequency was found that expressed higher levels of CD69 in PS19 mice on the MAITCAST vs. wildtype background, overall MAIT cell numbers in the brain did not differ between these groups. Interestingly, increased MR1 expression was detected on microglia only in PS19 mice, whereas MR1 was higher in PS19 and PS19/MAITCAST mouse astrocytes. Increased MAIT cell numbers did not alter tau accumulation or cognitive performance, whereas the lack of the MR1/MAIT cell axis did not affect tau burden, but was associated with reduced neuronal density and impaired recognition memory. Together, these findings suggest that the MR1/MAIT cell axis does not substantially influence the early development of tau pathology.