A novel unconventional T cell population enriched in Crohn's disease. Issue 11 (9th March 2022)

• Record Type: Journal Article
• Authors: Rosati, Elisa; Rios Martini, Gabriela; Pogorelyy, Mikhail V; Minervina, Anastasia A; Degenhardt, Frauke; Wendorff, Mareike; Sari, Soner; Mayr, Gabriele; Fazio, Antonella; Dowds, Christel Marie; Hauser, Charlotte; Tran, Florian; von Schönfels, Witigo; Pochhammer, Julius; Salnikova, Maria A; Jaeckel, Charlot; Gigla, Johannes Boy; Sabet, Sanaz Sedghpour; Hübenthal, Matthias; Schiminsky, Esther; Schreiber, Stefan; Rosenstiel, Philip C; Scheffold, Alexander; Thomas, Paul G; Lieb, Wolfgang; Bokemeyer, Bernd; Witte, Maria; Aden, Konrad; Hendricks, Alexander; Schafmayer, Clemens; Egberts, Jan-Hendrick; Mamedov, Ilgar Z; Bacher, Petra; Franke, Andre;
• Is Part Of: Gut. Volume 71:Issue 11(2022)
• Page Start: 2194
• Page End: 2204
• Publication Date: 2022-03-09
• Subjects: T-cell receptor -- alpha beta T cells -- Crohn's disease -- mucosal immunology -- IBD; Gastroenterology -- Periodicals; 616.33
• DOI: 10.1136/gutjnl-2021-325373
• Languages: English
• ISSNs: 0017-5749

Abstract

Abstract : 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.