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P041 Mesenchymal stem cells protect from acute dextran sulphate sodium-induced colitis by attenuating function of antigen presenting cells

V. Volarevic*, A. Nikolic, B. Simovic Markovic, M. Gazdic, I. Djordjevic, M. Dasic, N. Arsenijevic, M.L. Lukic

Faculty of Medical Sciences University of Kragujevac, Immunology, Kragujevac, Serbia

Background

Acute dextran sulphate sodium (DSS)-induced colitis is a well-established murine model of colitis, because of the high degree of uniformity, reproducibility and similarities to acute human colitis. DSS induces mucosal injury and inflammation which is accompanied with migration of inflammatory cells in the colon. Because of their immunomodulatory characteristics, mesenchymal stem cells (MSC) are considered as promising therapeutic agents for the therapy of immune mediated diseases. Recently published studies suggested therapeutic potential of MSC for the treatment of colitis, but the mechanisms remain unknown. The main aim of this study was to evaluate possible cellular targets of MSC in the pathology of acute colitis.

Methods

DSS (3%, molecular weight 40kDa) was dissolved in water and given to C57Bl/6 mice in place of normal drinking water (ad libitum) for 7 days. Mouse bone marrow-derived MSC (2 x 106 cells) were intravenously injected daily. Disease Activity Index (DAI: weight loss, stool consistency, visible blood in feces), was used to assess the clinical signs of colitis. The histology score of colitis was calculated as the sum of "infiltration" and "damage of epithelium" sub-scores for each mouse. The cellular make up of colon and phenotype of colon-infiltrated immune cells was determined by flow cytometry.

Results

DAI and histology score were significantly attenuated in DSS+MSC-treated mice (n=16) compared to DSS-only treated animals (n=16). This was associated with the reduced infiltration of innate immune cells in the colon, particularly antigen presenting cells (CD11c+CD11b+ inflammatory dendritic cells and F4/80+CD11b+macrophages). In addition, intravenous injection of MSC attenuate expression of major histocompatibility complex II and co-stimulatory molecules on antigen presenting cells. The percentage of protective CD3+NK1.1+ NKT cells and F480+CD206+ alternatively activated macrophages was higher in colons of DSS+MSC-treated mice compared to DSS-only treated animals. Injection of MSC did not affect infiltration and phenotype of CD45+Ly6G+CD11c- neutrophils, CD45+SinglecF+CD11c- eosinophils and FcERI+CD117+mast cells.

Conclusion

MSC attenuate function of inflammatory antigen presenting cells in colon and protect from acute DSS-induced colitis