DOP006 Gut-homing adipose tissue T-cells might influence intestinal barrier function in Crohn’s disease and obesity
L. J. Jödicke*1, L. I. Kredel1, A. A. Kuehl1, I. Freise1, J. Gröne2, J. Ordemann3, 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, 3Charité, Campus Mitte, Centre for Obesity and Metabolic Surgery, Berlin, Germany
Obesity (OB) is associated with adipose tissue inflammation, as well as impaired barrier function and intestinal inflammation. Whether adipose tissue inflammation itself influences barrier function remains to be clarified. Whereas OB mucosal barrier defects are minor, Crohn’s disease (CD) is characterised by destruction of the intestinal barrier. Adipose tissue inflammation is linked to CD, as the course of the disease is altered in obese CD patients, with higher complications and poor therapy response. In addition, inflammation of the mesenteric fat—better described as creeping fat (CF)—is a characteristic finding in CD. T-cells play an important role in pathogenesis and disease progression of OB and CD. Our aim was to analyse the gut-homing potential of T-cells in the intra-abdominal fat. We compared visceral fat (VF) from obese patients with CF from CD patients. VF from patients with ulcerative colitis (UC) and subcutaneous fat (SF) from obese patients served as controls.
Adipose tissue (5–10 g) was sampled from CD and UC patients during disease-related surgery and from obese patients undergoing bariatric surgery. Fractions were fixed for immune histological staining. Immune cells were isolated from the tissue and analysed by flow cytometry. The local ethic committee approved the study.
Significantly, more immune cells, and amongst them T-cells, infiltrate the CF, compared with all other tested fat tissues. More T-cells were found in VF of obese patients than in their SF. In CF CD4+-cells represent the main T-cell population (~60%). Similarly, in SF of OB CD4+cells are predominant, whereas the CD4/CD8 ratio is balanced in VF of OB and UC. About 50% of CD4+T-cells are within the VF of OBareintegrin alpha(α)4beta(β)7+, significantly more than within their SF. In the CF ~33% of CD4+T-cells are α4β7+, even less in VF of UC. α4β7-expressionis higher in CD8+cells especially in the VF of OB patients. About 25% of CD8+α4β7+T-cells co-expressed the resident-marker αE in the VF from OB.
T-cells are main players in inflammatory processes, effecting adipose tissue and intestinal inflammation in both CD and OB. In our study gut-homing α4β7+ T-cells were found in all tested adipose tissues, but they were strongly increased in VF of obese patients. The pro-inflammatory milieu within the VF might influence present T-cells. Therefore, it is tempting to speculate that these cells are involved in the impairment of the mucosal barrier in OB. Further, these adipose tissue primed α4β7+ T-cells might also be involved in the altered disease progression of obese CD patients. Further studies are needed to analyse the potential function of this interesting T-cell population.