Background & aims:
IL-17 producing lymphocytes can provide protective immunity during pathogenic infections yet their roles in inflammatory diseases are controversial. While they can sustain inflammation leading to tissue pathology, they also can contribute directly to or recruit other cell types involved in wound repair. These dual roles appear dependent on the context of disease and tissue, thus requiring further resolution. Mucosal-associated-invariant-T-(MAIT) cells are an innate-like group of T cells, which acquire a type III signature in the thymus. In this study, we dissected the in vivo role of MAIT cells in a spontaneous model of colitis from a genetically diverse mouse strain.
Methods: Multidimensional spectral flow cytometry and scRNAseq were used to characterize MAIT and immune cell dynamics and transcriptomic signatures respectively, in the collaborative-cross animal model, CC011/Unc and CC011/Unc-Traj33-/-.
Results:
Unlike many mouse laboratory strains, CC011 is a MAIT cell-rich mouse strain at steady-state. An age-dependent elevation in colonic MAIT, Thelper-17 and neutrophils coincided with the progression of spontaneous colitis and histological features that emulate human disease. The transcriptomic signature of colon MAIT cells included an activated profile indicative of their presence in an inflammatory environment and an enrichment for a type III signature. IL-17A was readily produced by colonic CC011 MAIT cells from diseased animals in vivo. In the MAIT cell deficient CC011 Traj33-/- strain, minimal colonic histopathology was observed and myeloperoxidase staining of the colon revealed a significant reduction of neutrophils.
Conclusions:
Our work suggests that MAIT cells are key mediators in the severity of disease and may regulate intestinal inflammation via the recruitment of neutrophils in the colon.