T-cell composition in ileal and colonic creeping fat - separating ileal from colonic Crohn´s disease.

Background & 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, 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, whereas 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 ten times more T-cells than colonic fat. The proportions of regulatory and central memory T-cells were significantly higher in ileal CF compared to 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.