MAIT cells drive chronic inflammation in a genetically diverse model of spontenous colitis

MAIT cells are innate-like T cells conserved across species and bridge innate and adaptive immunity. After T-cell receptor mediated stimulation, they rapidly produce a range of chemokines and inflammatory mediators and thus may contribute important roles in infection, autoimmunity and inflammatory diseases. MAIT cells are rare in many laboratory mice strains. The collaborative cross strain CC011/Unc has high numbers of MAIT cells at steady-state across the peripheral and lymphoid tissues. Strikingly, CC011 mice develop spontaneous colitis after 20 weeks of age. We explored the role of MAIT cells in the CC011 spontaneous colitis model. We used single cell RNA sequencing (scRNA-seq) to analyze the transcriptome of MAIT cells in the spleen and colon of diseased CC011 mice aged (28-30 week old). Overall design: MAIT cells were enriched by magnetic-bead MR1-5-OP-RU tetramer enrichment from spleen tissue prior to purified by Fluorescence-activated cell sorting (FACS). In the colon, MAIT cells were sort purified directly from enzymatically digested and percoll gradient separated colon tissue. Both tissues were analyzed using scRNAseq.