Inflammatory bowel diseases
Mucosal-associated invariant T (MAIT) cells play a central role in mucosal antimicrobial immunity by recognizing a finite variety of B vitamin precursors produced by bacteria common to the gut microbiome. Dysregulation of mucosal antimicrobial immunity is believed to be central to Crohn’s disease pathogenesis, however, little is known about intestinal MAIT cells in this condition. We used flow cytometry to analyze MAIT cells from the blood or colon biopsies of Crohn’s disease patients and healthy controls for mRNA transcriptome profiling and T cell receptor (TCR) sequencing. By flow cytometry, colonic MAIT cells in Crohn’s disease were not significantly different from healthy controls, regardless of inflammation, but did express less NKG2D, which contradicts what has been described in blood. At the mRNA level, MAIT cells overexpressed several immune-related genes relative to conventional CD8+ T cells. The most significant was the IL-23 receptor, which has been implicated in Crohn’s disease pathogenesis by genetic studies and clinical trials. MAIT cells also expressed more TNFRSF25 than conventional CD8+ T cells, where genetic polymorphisms of its ligand TNFSF15 have been associated with Crohn’s disease, particularly in Asia. Paired TCR sequencing was performed on single cell sorted MAIT cells from colon biopsies. In cells with a canonical MAIT TCR alpha chain rearrangement TRAV1-2/TRAJ12/20/33, we observed more TCR beta chain diversity in healthy controls than Crohn’s disease, regardless of mucosal inflammation. Additionally, we found considerable heterogeneity in the clonality of MAIT cells among all patients despite having limited antigens which are presented by the non-polymorphic MR1 molecule.