A novel unconventional T cell population enriched in Crohn's disease

One of the current hypotheses to explain the pro-inflammatory immune response in Crohn's disease (CD) is a dysregulated T cell reaction to yet unknown intestinal antigens. As such, it may be possible to identify disease-associated T cell clonotypes by analysing the peripheral and intestinal T-cell receptor (TCR) repertoire of CD patients and controls. We performed bulk TCR repertoire profiling of both the TCR alpha and beta chains using high-throughput sequencing for a total of 244 IBD patients' and healthy controls' peripheral blood samples as well as from matched blood and intestinal tissue of 59 IBD patients and controls. We identified a group of clonotypes, characterized by semi-invariant TCR alpha chains, to be significantly enriched in CD patients and particularly expanded in the CD8+ T cell population. These disease-associated cells were further classified classified through single-cell RNAseq, and TCRseq and flow cytometry analyses, as innate-like T cells with a comparable gene expression phenotype to unconventional T cells such as mucosal associated invariant T (MAIT) and natural killer T (NKT) cells, but with distinct TCRs. We thus identified and characterized a new subpopulation of innate-like semi-, Crohn associated invariant T cells, selectively enriched in Crohn's diseaseCD and that may have the potential to be used for applications into clinical practice as diagnostic markers and therapeutic targets in clinical practice.