DOP05 Adipose-derived stem cells from Crohn’s disease patients show antigen presenting cell-like properties

• Published in: Journal of Crohn's and colitis Vol. 13; no. Supplement_1; p. S030
• Main Authors: Serena, C, Terrón-Puig, M, Ejarque, M, Algaba-Chueca, F, Maymó-Masip, E, Millan, M, Menacho, M, Espin, E, Martí, M, Fernández-Veledo, S, Vendrell, J
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 25.01.2019
• ISSN: 1873-9946; 1876-4479
• DOI: 10.1093/ecco-jcc/jjy222.040

Abstract Background Under physiological conditions, mesenchymal stem cells (MSCs) are known to modulate the function of diverse types of immune cells, both adaptive and innate. However, only recently has their role in an inflammatory microenvironment undergone scrutiny. In this sense, our group reveals that MSCs isolated from adipose tissue (called adipose-derived stem cells; ASCs) from Crohn’s disease (CD) patients are immune activated (showing a high inflammatory profile, high invasive and phagocytic capacities and worse immunosupressive properties). So, our hypothesis is that in CD, ASCs within the creeping fat (CF) and also the mesentery (MES) are tightly stacked in a chronic inflammatory milieu, which may cause their enforced expression of Class II major histocompatibility complex (MHC) due to an inappropriate response to intestinal dysbiotic microbiota. Methods Donors are being recruited at Hospital Joan XXIII of Tarragona and Hospital Vall d’Hebron of Barcelona in accordance with the principles of the Helsinki Declaration. ASCs were isolated from adipose tissue biopsies of visceral origin: CF and MES in Crohn subjects (n = 6) and MES in no-Crohn subjects (n = 6). Groups were matched by age, gender, and BMI. Antigen-presenting cell properties were studied by flow cytometer, gene expression and immunofluorescence in ASCs of Crohn vs. no-Crohn subjects. Results Significant differences in the surface expression of human leucocyte antigen–DR isotype (HLA-DR) and the costimulatory molecule 86 (CD86) were observed between ASCs isolated from Crohn vs. no-Crohn subjects (Figure 1A and B). Interestingly, all ASCs were able to uptake ovalbumin (OVA) when we administered to the cell (Figure 1C). Furthermore, multiple genes involved in MHCII antigen processing and presentation increased in ASCs isolated from Crohn patients (Figure 1D). Figure 1. Adipose-derived stem cells from Crohn's disease patients function as antigen-presenting cells. (A) Adipose-derived stem cells (ASCs) obtained from 6 no-Crohn and 6 Crohn donors and stained with the panel of antibodies and analysed by flow cytometry on the FACS ARIA III cytometer (BD). (B) Representative histogram of HLA-DR in ASCs of Crohn and no-Crohn subjects. (C) Fluorescence representative image of OVA uptake by ASCs. (D) Gene expression of antigen presentation markers in ASCs isolated from Crohn and no-Crohn subjects. *p < 0.05 vs. no-Crohn subjects. No parametric test (U-Mann Whitney). Conclusions Our investigation highlights a role of ASCs as antigen-presenting cell in CD subjects promoting the immune system activation, influencing CD outcome and disease progression.