Abstract
BackgroundAtherosclerosis (AS) presents characteristic of a chronic inflammatory disease in which both adaptive and innate immune cells play roles. Accumulating evidence has showed the impairment of natural killer (NK) cells in atherosclerosis, however, the mechanisms of this impairment remain unclear. In this study, we investigated the expression of CD160 on NK cells and assessed its pathological roles in NK loss during atherogenesis.MethodsCD160 expression on NK cells was measured in 49 AS patients and 41 healthy controls (HC) by flow cytometry, their inflammatory cytokine levels in sera were determined by ELSIA, and the effect of CD160 engagement on NK cells was evaluated by in vitro culture experiments.ResultsCompared to HC, AS patients had a significantly increased CD160 expression on peripheral NK cells and concomitantly decreased peripheral NK cell number, and increased CD160 expression was positively related to the levels of serum lipids and IFN-γ, TNF-α and IL-6 inflammation cytokines, which all are risk factors for atherogenesis, and inversely correlated with peripheral NK cell number. Furthermore, engagement of CD160 receptor on NK cells from AS patients triggers a significantly increased production of inflammation cytokines and subsequent NK cell apoptosis, and blockade of TNF-α prevented the increased apoptosis of NK cells from AS patients after CD160 engagement, indicating a critical role of TNF-α in mediating NK cell loss by CD160 engagement.ResultsOur results provide evidence that elevated CD160 expression on NK cells plays an important role in NK cell loss in atherosclerosis. The increased CD160 expression on NK cells might be used as an indicator for disease progression.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0564-3) contains supplementary material, which is available to authorized users.
Highlights
Atherosclerosis (AS) presents characteristic of a chronic inflammatory disease in which both adaptive and innate immune cells play roles
Increased CD160 expression on natural killer (NK) cells from AS patients To explore the potential involvement of CD160 in atherogenesis, we first compared CD160 expression levels in AS patients and the healthy controls (HC)
Flow cytometric analysis detected a low level of CD160 expression on both CD3+CD8+ and CD3+CD8− T cells as previously reported [25]; no difference in the percentage and mean fluorescence intensity (MFI) of CD160 expression within these cells was observed between the AS patients and HC (Figure 1b; Additional file 2: Figures S2A, S1B)
Summary
Atherosclerosis (AS) presents characteristic of a chronic inflammatory disease in which both adaptive and innate immune cells play roles. It was shown that deficiency of functional NK cells significantly reduced the size of atherosclerosis in Ly49A transgenic mice, suggesting a proatherogenic property for NK cells in atherosclerosis development [8] These conflicting results may be partially explained by the fact that beige mutation or Ly49A transgene influences the functions of other immune cells [11–14], making it difficult to clearly define the role of NK cells in the pathogenesis of atherosclerosis. By depleting or repleting NK cells in atherosclerosis-prone ApoE-deficient (ApoE−/−) mice, Selathurai et al showed that NK cells promote atherosclerosis in a cytotoxicity-dependent manner [11]. Despite these studies, it remains to explore the detailed molecular mechanisms for the involvement of NK cells in atherosclerosis
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