Myeloid cell regulation by CD200 signalling in atherosclerosis

Abstract Background: Atherosclerosis, the major risk factor for cardiovascular disease and the leading cause of death worldwide, is a multifactorial chronic inflammatory disease. CD200 is reported to be an endogenous myeloid suppressor. Deletion of CD200 in vivo increases myeloid cell numbers and activation resulting in enhanced susceptibility to autoimmune diseases and infection. However, the importance of CD200 in atherosclerosis development is still unknown. Methods and Results: To understand the role of CD200 signalling, both the effect of CD200 deletion and provision were assessed in a murine model of atherosclerosis. Firstly, CD200-deficient (CD200-/-) mice were crossed with apolipoprotein E deficient (ApoE-/-) mice. CD200 deficiency accelerates advanced atherosclerotic lesion formation in the aortic roots, as shown by the morphometric measurement of aortic root atherosclerotic lesion development. Moreover, the leukocyte content of various tissues was assessed by flow cytometry. APOE-/-CD200-/- mice exhibit significant increase in specific myeloid cell populations in spleen, blood and aorta. Secondly, the role of CD200R ligation has been examined in a murine model of carotid injury. ApoE-/-mice underwent surgery for placement of a perivascular collar and were treated with 10mg/kg of a CD200-Fc fusion protein. Three weeks post injury, carotid arteries were removed and neointima formation was assessed. CD200-Fc fusion protein treatment attenuated neointima development. Interestingly, CD200-Fc fusion protein affects macrophage accumulation and polarization. Conclusions: Our data indicate that CD200 is an important modulator of myeloid cell function and phenotype in atherosclerosis and suggest that targeting the CD200-CD200R pathway holds promise as a potential therapeutic strategy in atherosclerosis.