Colonic mucosal associated invariant T cells in Crohn’s disease have a diverse and non-public T cell receptor beta chain repertoire

• Published in: PloS one 2023-11, Vol.18 (11), p.e0285918-e0285918
• Main Authors: Konecny, Andrew J, Shows, Donna M, Lord, James D
• Format: Article
• Language: English
• Subjects: Antibodies; Bacterial infections; Biology and Life Sciences; Biopsy; Blood; Care and treatment; CD8 antigen; Cloning; Colon; Comparative analysis; Crohn's disease; Cytokines; Diagnosis; Enrichment; Flow cytometry; Genes; Genomes; Health aspects; Heterogeneity; Infections; Inflammation; Inflammatory bowel disease; Intestinal microflora; Invariants; Lamina propria; Lymphocytes; Lymphocytes T; Medicine and Health Sciences; Microbiomes; Mucosa; Pancreatic beta cells; Pathogenesis; Patients; Phenotypes; Precursors; Receptors; Riboflavin; T cell receptors; T cells; Transcriptomes; Tuberculosis; Viral infections
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0285918

Mucosal-Associated Invariant T (MAIT) cells are T cells with a semi-invariant T cell receptor (TCR), recognizing riboflavin precursors presented by a non-polymorphic MR1 molecule. As these precursors are produced by the gut microbiome, we characterized the frequency, phenotype and clonality of MAIT cells in human colons with and without Crohn's disease (CD). The transcriptome of MAIT cells sorted from blood and intestinal lamina propria cells from colectomy recipients were compared with other CD8.sup.+ T cells. Colon biopsies from an additional ten CD patients and ten healthy controls (HC) were analyzed by flow cytometry. TCR genes were sequenced from individual MAIT cells from these biopsies and compared with those of MAIT cells from autologous blood. MAIT cells in the blood and colon showed a transcriptome distinct from other CD8 T cells, with more expression of the IL-23 receptor. MAIT cells were enriched in the colons of CD patients, with less NKG2D in inflamed versus uninflamed segments. Regardless of disease, most MAIT cells expressed integrin [alpha]4[beta]7 in the colon but not in the blood, where they were enriched for [alpha]4[beta]7 expression. TCR sequencing revealed heterogeneity in the colon and blood, with few public sequences associated with cohorts. MAIT cells are enriched in the colons of CD patients and disproportionately express molecules (IL-23R, integrin [alpha]4[beta]7) targeted by CD therapeutics, to suggest a pathogenic role for them in CD. Public TCR sequences were neither common nor sufficiently restricted to a cohort to suggest protective or pathogenic antigen-specificities.