title: High endothelial venules associated with T cell subsets in the inflamed gut of newly diagnosed inflammatory bowel disease patients.
abstract: Naive and central memory T lymphocytes (TNand TCM) can infiltrate the inflamed gut mucosa in inflammatory bowel disease (IBD) patients. Homing of these subsets to the gut might be explained by ectopic formation of tertiary lymphoid organs (TLOs), containing high endothelial venules (HEVs). We aimed to evaluate the presence of HEVs and TLOs in inflamed intestinal mucosa of newly diagnosed, untreated IBD patients in relation to the presence of TNand TCMlymphocytes. IBD patients (n = 39) and healthy controls (n = 8) were included prospectively. Biopsy samples of inflamed and normal intestine, respectively, were analysed by immunohistochemistry for lymphocytes (CD3/CD20), blood vessels (CD31) and peripheral lymph node addressin (PNAd) expression (MECA-79). TNand TCMlymphocyte subsets were identified by flow cytometric immunophenotyping. A higher number of HEVs was found in the inflamed colon of patients with ulcerative colitis [median 3·05 HEV/mm2; interquartile range (IQR) = 0-6·39] and ileum of Crohn's disease patients (1·40; 0-4·34) compared to healthy controls (both 0; P = 0·033). A high density of colonic HEVs (HEVhigh) was associated with increased infiltration of TNand TCMin the inflamed gut (median 87%; IQR = 82-93% of T cell population), compared to HEVlowpatients (58%; 38-81%; P = 0·003). The number of colonic follicles was higher in HEVhighpatients (median 0·54/mm2; IQR 0·28-0·84) compared to HEVlowpatients (0·25/mm2; 0·08-0·45; P = 0·031) and controls (0·31/mm2; 0·23-0·45; P = 0·043). Increased homing of TNand TCMlymphocytes to inflamed gut tissue in IBD patients might be facilitated by ectopic formation of extrafollicular HEVs and TLOs in a subgroup of patients.
authors.affiliation: Department of Gastroenterology and Hepatology, Rijnstate Hospital, Arnhem, the Netherlands.
authors.forename: C S
authors.initials: CS
authors.lastname: Horjus Talabur Horje
authors.affiliation: Department of Gastroenterology and Hepatology, Rijnstate Hospital, Arnhem, the Netherlands.
authors.forename: C
authors.identifier: 0000-0003-0401-8761
authors.initials: C
authors.lastname: Smids
authors.affiliation: Department of Pathology, Rijnstate Hospital, Arnhem, the Netherlands.
authors.forename: J W R
authors.initials: JW
authors.lastname: Meijer
authors.affiliation: Department of Gastroenterology and Hepatology, Rijnstate Hospital, Arnhem, the Netherlands.
authors.forename: M J
authors.initials: MJ
authors.lastname: Groenen
authors.affiliation: Department of Pathology, Rijnstate Hospital, Arnhem, the Netherlands.
authors.forename: M K
authors.initials: MK
authors.lastname: Rijnders
authors.affiliation: Department of Microbiology and Immunology, Rijnstate Hospital, Arnhem, the Netherlands.
authors.forename: E G
authors.initials: EG
authors.lastname: van Lochem
authors.affiliation: Department of Gastroenterology and Hepatology, Rijnstate Hospital, Arnhem, the Netherlands.
authors.forename: P J
authors.initials: PJ
authors.lastname: Wahab
mesh_terms: D000328:Adult; D015415:Biomarkers; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016130:Immunophenotyping; D015212:Inflammatory Bowel Diseases / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000098:blood supply* / Q000473:pathology*; D018655:Lymphocyte Count; D008297:Male; D009389:Neovascularization, Pathologic; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D014699:Venules / Q000473:pathology*; D055815:Young Adult
chemical_list: D015415:Biomarkers
keywords: T lymphocytes; high endothelial venules; inflammatory bowel disease; lymphocyte homing; tertiary lymphoid organ