A032 Specific overexpression of FcgRIIb on macrophages reduces atherosclerosis in LDLr deficient mice

Fc receptors for IgG are key players in regulating innate and adaptive immunity. Activation of Fc receptor triggers phagocytosis, inflammatory cytokine-release, antigen presentation, and regulation of humoral responses. FcgRIIb plays a unique role in negatively regulating immune responses. Atherosclerosis is an inflammatory disease in which monocytes/macrophages are deeply involved. The generation of mice overexpressing FcgRIIb on macrophages (M-TG) allowed us to explore the specific role of macrophages FcgRIIb expression in the development of atherosclerosis. To this end, we reconstitued lethally irradiated LDLr-deficient mice with bone marrow cells of either control or M-TG and after 4weeks of recovery mice have been subjected to high fat diet during 11 weeks to induce atherogenesis. Our results show that LDLr -/- mice reconstitued with bone marrow of M-TG have 21 % reduction of atherosclerotic plaque size in aortic sinus in comparison with control (p=0.01) despite a similar cholesterol level in both groups and the development of very advanced lesions. CD3-stimulated splenic T cells isolated from M-TG mice produced 46 % less IFNg (P These results clearly show that FcgRIIb overexpression on macrophages reduces atherosclerosis plaque development by triggering a phenotype shift of immune cells involved in atherosclerosis. Additional experiments are ongoing to understand mechanisms that induce T cell modulation.