Triggering Receptor Expressed on Myeloid Cells 1 (TREM-1) Activation Increases the Production of Pro-Inflammatory Cytokines by Inflammatory Bowel Disease Mucosa

AMMOSCATO F; BIANCHERI P; KUCIK A; BELL I; CURCIARELLO R; KRUIDENIER L; MACDONALD TT

Vancouver, BC

Congreso; 16th International Congress of Mucosal Immunology; 2013

Society of Mucosal Immunology

Background and Aim: Intestinal macrophages play an important role in the pathogenesis of inflammatorybowel disease (IBD). Inflamed IBD mucosa contains high numbers of CD33+CD68+ macrophagesoverexpressing Triggering receptor expressed on myeloid cells 1 (TREM-1). We explored the ex vivoeffects of a TREM-1 activating antibody on the intestinal immune response in IBD. Material and Methods:The expression of CD68, CD33 and TREM-1 was analysed by flow cytometry on lamina propriamononuclear cells isolated from inflamed colon of 11 IBD patients and normal colon of eight controlsubjects. Inflamed IBD biopsies were cultured ex vivo with or without an activating anti-TREM-1monoclonal antibody, and the production of interleukin (IL)-1b, IL-6 and IL-8 was determined by ELISA.Results: The percentage of mucosal CD33+CD68+ macrophages was significantly higher in IBD comparedto control subjects. TREM-1 expression by mucosal macrophages was significantly higher in IBDcompared to control subjects. TREM-1 activation significantly increased IL-1b, IL-6 and IL-8 production byIBD biopsies cultured ex vivo. Conclusions: TREM-1 is overexpressed on IBD mucosal macrophages,and its activation amplifies pro-inflammatory cytokine production. Further studies using chromatinimmunoprecipitation assays are under way in order to establish whether TREM-1 overexpression in IBDmay derive from epigenetic changes.