Lea I Kredel1, Lisa J Jödicke1, Alexander Scheffold2, Jörn Gröne3,4, Rainer Glauben1, Ulrike Erben1,5, Anja A Kühl1,5, Britta Siegmund1. 1. Medical Department, Division of Gastroenterology, Infectiology and Rheumatology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany. 2. Medical Department [Rheumatology, Clinical Immunology], Department of Cellular Immunology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany. 3. Department of Surgery, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany. 4. Department of Surgery, Rotes Kreuz Krankenhaus Bremen, Bremen, Germany. 5. iPATH, Core Unit/Research Center ImmunoSciences, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
Abstract
BACKGROUND AND AIMS: Creeping fat [CF] is a hyperplasia of adipose tissue adjacent to inflamed intestine in Crohn's disease [CD]. Data from genome-wide association studies [GWAS] distinguished Crohn's colitis from ileal CD and ulcerative colitis [UC]. This study analysed the T-cell compartments of ileal and colonic mesenteric fat and corresponding mucosa to provide cellular proof for the suggested GWAS classification. METHODS: Samples were obtained from 34 CD or UC patients. Cells were analysed by immunohistochemistry and flow cytometry, and tissue cytokine release was assessed by cytometric bead array. RESULTS: Only ileal CF revealed the distinct adipocyte hyperplasia combined with dense T-cell infiltration and fibrosis; colonic fat from CD and UC patients lacked these findings. T-cell subpopulations differed between mesenteric fat in ileal CD, colonic CD and UC: ileal CF had nearly 10 times more T-cells than colonic fat. The proportions of regulatory and central memory T-cells were significantly higher in ileal CF compared with colonic fat in CD and UC. In all groups, the mucosal T-cell compartment was distinct from the mesenteric fat. Remarkably, correlation between disease activity and proportion of pro- and anti-inflammatory T-cell subpopulations was inverse, comparing ileal and colonic fat in CD. CONCLUSIONS: This first in-depth analysis of the T-cell compartment in ileal and colonic mesenteric adipose tissue in CD and UC identifies a unique T-cell niche in the ileal mesenteric fat tissue in CD. From a clinical point of view, our findings underscore the novel concept of colonic and ileal CD as distinct IBD entities.
BACKGROUND AND AIMS: Creeping fat [CF] is a hyperplasia of adipose tissue adjacent to inflamed intestine in Crohn's disease [CD]. Data from genome-wide association studies [GWAS] distinguished Crohn's colitis from ileal CD and ulcerative colitis [UC]. This study analysed the T-cell compartments of ileal and colonic mesenteric fat and corresponding mucosa to provide cellular proof for the suggested GWAS classification. METHODS: Samples were obtained from 34 CD or UC patients. Cells were analysed by immunohistochemistry and flow cytometry, and tissue cytokine release was assessed by cytometric bead array. RESULTS: Only ileal CF revealed the distinct adipocyte hyperplasia combined with dense T-cell infiltration and fibrosis; colonic fat from CD and UC patients lacked these findings. T-cell subpopulations differed between mesenteric fat in ileal CD, colonic CD and UC: ileal CF had nearly 10 times more T-cells than colonic fat. The proportions of regulatory and central memory T-cells were significantly higher in ileal CF compared with colonic fat in CD and UC. In all groups, the mucosal T-cell compartment was distinct from the mesenteric fat. Remarkably, correlation between disease activity and proportion of pro- and anti-inflammatory T-cell subpopulations was inverse, comparing ileal and colonic fat in CD. CONCLUSIONS: This first in-depth analysis of the T-cell compartment in ileal and colonic mesenteric adipose tissue in CD and UC identifies a unique T-cell niche in the ileal mesenteric fat tissue in CD. From a clinical point of view, our findings underscore the novel concept of colonic and ileal CD as distinct IBD entities.
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