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

2022; BMJ; Volume: 71; Issue: 11 Linguagem: Inglês

10.1136/gutjnl-2021-325373

1468-3288

Elisa Rosati, Gabriela Rios Martini, Mikhail V. Pogorelyy, Anastasia A. Minervina, Frauke Degenhardt, Mareike Wendorff, Soner Sarı, Gabriele Mayr, Antonella Fazio, C. Marie Dowds, Charlotte A. E. 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 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 Bächer, André Franke,

IL-33, ST2, and ILC Pathways

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.