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.

CEITEC Masaryk University Brno Czech Republic

Center for Precision Genome Editing and Genetic Technologies for Biomedicine Moscow Russian Federation

Department of Dermatology University Hospital Schleswig Holstein Kiel Schleswig Holstein Germany

Department of General Surgery Rostock University Medical Center Rostock Mecklenburg Vorpommern Germany

Department of Immunology St Jude Children's Research Hospital Memphis Tennessee USA

Department of Internal Medicine 1 Universitätsklinikum Schleswig Holstein Kiel Schleswig Holstein Germany

Department of Visceral and Thoracic Surgery Universitatsklinikum Schleswig Holstein Kiel Schleswig Holstein Germany

Dmitry Rogachev National Research Center of Pediatric Hematology Moscow Russian Federation

Institute of Clinical Molecular Biology Christian Albrechts University of Kiel Kiel Schleswig Holstein Germany

Institute of Epidemiology and Biobank POPGEN Christian Albrechts University of Kiel Kiel Germany

Institute of Immunology Christian Albrechts University of Kiel Kiel Schleswig Holstein Germany

Interdisciplinary Crohn Colitis Centre Minden Minden Germany

Shemyakin Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Sciences Moscow Russian Federation

Gut. 2023 Dec 7;73(1):205-206. doi: 10.1136/gutjnl-2022-328684. PubMed

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