Abstract
Neutrophils constitute abundant cellular components in atherosclerotic plaques. Most of the current studies are focused on the roles of granular proteins released by neutrophils in atherosclerosis. Here, we revealed a unique subset of neutrophils which exhibit the characteristics of antigen-presenting cell (APC) (which were called APC-like neutrophils afterwards) in atherosclerosis. The roles of APC-like neutrophils and relevant mechanisms were investigated in hyperlipidemic patients and atherosclerotic mice. Higher percentages of neutrophils and APC-like neutrophils were found in peripheral blood of hyperlipidemic patients than that of healthy donors. Meanwhile, we also identified higher infiltration of neutrophils and APC-like neutrophils in atherosclerotic mice. Ox-LDL induced Phorbol-12-myristate-13-acetate (PMA)-activated neutrophils to acquire the APC-like phenotype. Importantly, upon over-expression of APC-like markers, neutrophils acquired APC functions to promote the proliferation and interferon-γ production of CD3+ T cells via HLA-DR/CD80/CD86. In accordance with what found in vitro, positive correlation between neutrophils and CD3+ T cells was observed in hyperlipidemic patients. In conclusion, our work identifies a proinflammatory neutrophil subset in both hyperlipidemic patients and atherosclerotic mice. This unique phenotype of neutrophils could activate the adaptive immune response to promote atherosclerosis progression. Thus, this neutrophil subset may be a new target for immunotherapy of atherosclerosis.
Highlights
Atherosclerosis is a chronic inflammatory disease that occurs in the walls of blood vessels, and is the pathological basis for cardiovascular diseases [1]
We have identified a unique neutrophil subset which expresses antigen-presenting cell (APC) associated markers including HLA-DR/ major histocompatibility complex (MHC)-II(mice), CD80 and CD86
We show that the percentage of APC-like neutrophils significantly increases both in hyperlipidemic patients and atherosclerotic mice
Summary
Atherosclerosis is a chronic inflammatory disease that occurs in the walls of blood vessels, and is the pathological basis for cardiovascular diseases [1]. Antigen presenting cells (APCs) are required for the priming of adaptive immune system [30]. APCs uptake and present antigens to T cells, triggering the adaptive immune response [31]. APClike neutrophils gain the ability to activate T cells, resulting in the production of inflammatory cytokines, and promote or dampen disease progression. Whether APC-like neutrophils exist in atherosclerotic plaques and the potential roles of this unique neutrophil subset in atherosclerosis are of great importance for further understanding of this inflammatory disease. We show that APC-like neutrophil subset exists in peripheral blood of hyperlipidemic patients and atherosclerotic plaques of LDLr-/- mice. Clinical data show a positive correlation between APC-like neutrophils and CD3+T cells, which implies APC-like neutrophils may promote atherosclerosis progression through activating adaptive immune system
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