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


Elisa Rosati, Gabriela Rios Martini, Mikhail Pogorelyy, Anastasia Minervina, Frauke Degenhardt, Mareike Wendorff, Soner Sari, Gabriele Mayr, Antonella Fazio, Christel Dowds, Charlotte Hauser, Florian Tran, Witigo Schönfels, Julius Pochhammer, Maria Salnikova, Charlot Jaeckel, Johannes Gigla, Sanaz Sabet, Matthias Hübenthal, Esther Schiminsky, Stefan Schreiber, Philip Rosenstiel, Alexander Scheffold, Paul Thomas, Wolfgang Lieb, Bernd Bokemeyer, Maria Witte, Konrad Aden, Alexander Hendricks, Clemens Schafmayer, Jan-Hendrick Egberts, Ilgar Mamedov, Petra Bacher, Andre Franke








OBJECTIVE: One of the current hypotheses to explain the proinflammatory immune response in IBD 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 patients with IBD and controls. DESIGN: We performed bulk TCR repertoire profiling of both the TCR alpha and beta chains using high-throughput sequencing in peripheral blood samples of a total of 244 patients with IBD and healthy controls as well as from matched blood and intestinal tissue of 59 patients with IBD and disease controls. We further characterised specific T cell clonotypes via single-cell RNAseq. RESULTS: We identified a group of clonotypes, characterised by semi-invariant TCR alpha chains, to be significantly enriched in the blood of patients with Crohn’s disease (CD) and particularly expanded in the CD8(+) T cell population. Single-cell RNAseq data showed an innate-like phenotype of these cells, with a comparable gene expression to unconventional T cells such as mucosal associated invariant T and natural killer T (NKT) cells, but with distinct TCRs. CONCLUSIONS: We identified and characterised a subpopulation of unconventional Crohn-associated invariant T (CAIT) cells. Multiple evidence suggests these cells to be part of the NKT type II population. The potential implications of this population for CD or a subset thereof remain to be elucidated, and the immunophenotype and antigen reactivity of CAIT cells need further investigations in future studies.