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

Elisa Rosati, Gabriela Rios Martini, Mikhail V Pogorelyy, Anastasia A Minervina, Frauke Degenhardt, Mareike Wendorff, Soner Sari, Gabriele Mayr, Antonella Fazio, Christel Marie Dowds, Charlotte Hauser, Florian Tran, Witigo von Schönfels, Julius Pochhammer, Maria A Salnikova, Charlot Jaeckel, Johannes Boy Gigla, Sanaz Sedghpour Sabet, Matthias Hübenthal, Esther Schiminsky, Stefan Schreiber, Philip C Rosenstiel, Alexander Scheffold, Paul G Thomas, Wolfgang Lieb, Bernd Bokemeyer, Maria Witte, Konrad Aden, Alexander Hendricks, Clemens Schafmayer, Jan-Hendrick Egberts, Ilgar Z Mamedov, Petra Bacher, Andre Franke
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Gut : journal of the British Society of Gastroenterology
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<h4>Objective</h4>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.<h4>Design</h4>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.<h4>Results</h4>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<sup>+</sup> 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.<h4>Conclusions</h4>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.