A032 Specific overexpression of FcgRIIb on macrophages reduces atherosclerosis in LDLr deficient mice - 17/04/09
Résumé |
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<0.01) than CD4+ T cells from control mice but same levels of IL4. There was no difference in the ability of regulatory T cells (Tregs) to inhibit effector CD4+ cells proliferation. However, using flow cytometry we found a 34 % increase of Tregs (CD4+, CD25+, Foxp3+) among CD4+ cells in LDLr-/- M-TG mice compared to control mice (p<0.01).
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.
Le texte complet de cet article est disponible en PDF.Vol 102 - N° S1
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