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The role of high-density lipoprotein in the regulation of the immune response: implications for atherosclerosis and autoimmunity

Journal

IMMUNOLOGY
Volume 164, Issue 2, Pages 231-241

Publisher

WILEY
DOI: 10.1111/imm.13348

Keywords

atherosclerosis; high‐ density lipoprotein; immune response; lipid metabolism

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Inflammation and immune dysfunction play crucial roles in the development of atherosclerosis. Low HDL levels are associated with both atherosclerosis and autoimmune rheumatic diseases, suggesting a potential link between the two. HDL modulates immune responses by affecting cholesterol transport and lipid raft disruption, predominantly showing anti-inflammatory effects despite some pro-inflammatory actions.
Inflammation and immune dysfunction have been increasingly recognized as crucial mechanisms in atherogenesis. Modifications in cell lipid metabolism, plasma dyslipidaemia and particularly low high-density lipoprotein (HDL) levels occur both in atherosclerosis and in autoimmune rheumatic diseases (which are strongly associated with an increased risk of atherosclerosis), suggesting the presence of a crucial link. HDL, the plasma lipoprotein responsible for reverse cholesterol transport, is known for its several protective effects in the context of atherosclerosis. Among these, HDL immunomodulatory effects are possibly the less understood. Through the efflux of cholesterol from plasma cell membranes with the consequent disruption of lipid rafts and the interaction with the cholesterol transporters present in the plasma membrane, HDL affects both the innate and adaptive immune responses. Animal and human studies have demonstrated a predominance of HDL anti-inflammatory effects, despite some pro-inflammatory actions having also been reported. The HDL role on the modulation of the immune response is further suggested by the detection of low levels together with a dysfunctional HDL in patients with autoimmune diseases. Here, we review the current knowledge of the immune mechanisms of atherosclerosis and the modulatory effects HDL may have on them.

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