The inhibitory FcγRIIb modulates the inflammatory response and influences atherosclerosis in male apoE< sup>−/−</sup> mice
YV Mendez-Fernandez, BG Stevenson, CJ Diehl... - Atherosclerosis, 2011 - Elsevier BACKGROUND: Atherosclerosis is widely accepted as an inflammatory disease involving both innate and adaptive immunity. B cells and/or antibodies have previously been shown to play a protective role against atherosclerosis. Aside from their ability to bind to antigens, ...
Atherosclerosis is widely accepted as an inflammatory disease involving both innate and adaptive immunity. B cells and/or antibodies have previously been shown to play a protective role against atherosclerosis. Aside from their ability to bind to antigens, antibodies can influence inflammatory responses by interacting with various Fcγ receptors on the surface of antigen presenting cells. Although studies in mice have determined that stimulatory Fcγ receptors contribute to atherosclerosis, the role of the inhibitory Fcγ receptor I Ib (FcγRI Ib) has only recently been investigated.
To determine the importance of FcγRI Ib in modulating the adaptive immune response to hyperlipidemia, we generated FcγRI Ib-deficient mice on the apo E-deficient background (apo E/FcγRI Ib / ). We report that male apo E/FcγRI Ib / mice develop exacerbated atherosclerosis that is independent of lipid levels, and is characterized by increased antibody titers to modified LDL and pro-inflammatory cytokines in the aorta.
These findings suggest that antibodies against atherosclerosis-associated antigens partially protect against atherosclerosis in male apo E / mice by conveying inhibitory signals through the FcγRI Ib that downregulate pro-inflammatory signaling via other immune receptors. These data are the first to describe a significant in vivo effect for FcγRI Ib in modulating the cytokine response in the aorta in male apo E / mice.
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The inhibitory FcγRIIb modulates the inflammatory response and influences atherosclerosis in male apoE< sup>−/−</sup> mice |
