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* = Presenting author

P061 Creeping fat contains a unique T-cell compartment with potential impact on intestinal inflammation

L. I. Kredel*1, L. J. Jödicke1, A. A. Kuehl1, I. Freise1, J. Gröne2, B. Siegmund1

1Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Gastroenterology, Infectiology and Rheumatology, Berlin, Germany, 2Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, General, Vascular and Thoracic Surgery, Berlin, Germany

Background

A hyperplasia of the mesenteric fat adjacent to the inflamed segments of the intestine—the creeping fat (CF)—is characteristic for Crohn’s disease (CD). Although it has been observed for decades, its function is not fully understood. Immune cells suh as T-cells accumulate in CF. Although their importance in mucosal immunology is evident, the composition, as well as the effect of adipose tissue T-cells (ATT) is unclear. This study compares T-cell subpopulations in CF and mucosa of CD patients: differences between CD colitis and ileal disease, as well as alterations in patients treated with steroids, were studied. Mesenteric fat and mucosa from ulcerative colitis (UC) patients served as control.

Methods

Mesenteric fat and mucosa were collected from CD and UC patients undergoing surgery because of disease-related complications. Small fractions were fixed for immune histological staining. T-cells from both compartments were analysed by flow cytometry. The study was approved by the local ethics committee.

Results

Significantly more T-cells infiltrate CF compared with mesenteric fat of UC patients. Besides the distinct difference in ATT numbers in CD and UC; the distribution of natural killer T (NKT) cells is noticeable: in CD more NKT are found in CF; however, in UC they are more frequent in the mucosa. CD4+cells are predominant in CF. Amongst these, the percentage of Th1-cells is higher while Treg and Th17 numbers are lower compared with mucosa. Differences can also be found regarding T-cell activation. Here, effector memory T-cells (TEM) are predominant in the CF; further, CD8+CD45RA+ TEM and naive T-cells are more abundant. Remarkably, the ATT compartment in CD differs depending on its location. Whereas mesenteric fat from CD colitis harbours generally more CD4+cells, IL-17+, Treg and TCRγδ are more frequent in the ileal CF. ATT are affected by steroid treatment. The percentage of CD4+ cells in ileal mesenteric fat is increased in patients on steroids, whereas it is decreased in steroid-treated UC patients. Further, the memory status of ATT is altered in steroid-treated patients.

Conclusion

Both the mucosa and CF of CD patients contain high numbers of (memory) T-cells, but with significantly different T-cell subpopulations, supporting the idea of an independent role of fat tissue in CD. Because disease progression differs in CD colitis and ileal disease, it is interesting that there is also a significant difference between the cellular compartments of the corresponding CF. An insight of the meaning of adipose tissue in CD might contribute to a better understanding of the disease. Further, since steroid treatment not only alters inflammatory processes within the mucosa but also affects ATTs, CF might become a factor in therapeutic considerations prospectively.