Natural Killer T cells and the invariant subset promote atherosclerosis: A meta-analysis.

Aims: Natural Killer T (NKT) cells are reported to be both pro- and anti-atherosclerotic. With this meta-analysis, we evaluated the NKT population and their subsets in regulating the atherosclerotic disease in mice.

Main Methods: Eighteen pre-clinical (mice, n = 1276) and 6 clinical observational studies (humans, n = 116) met the eligibility criteria for inclusion. Random effects model was used and standard mean difference (SMD) was calculated for the cell counts and aortic lesion area.

Key Findings: Lesion area decreased in the absence of whole NKT cell population (-1.33[95%CI, -2.14, -0.52]), and in the absence of only iNKT subset (-0.66[95%CI, -1.69, 0.37]). However, lesion area increased after over-expression/activation of iNKTs (1.40[95%CI, 0.28, 2.52]). Atherogenic diet (AD) or high fat diet (HFD) increased the number of NKT cells (2.51[95%CI, 1.42, 3.61]), whereas the iNKT cell numbers and iNKT cell-specific gene expression decreased in mice (-2.04[95%CI, -3.34, -0.75]) and atherosclerotic patients (-1.81[95 % CI, -2.89, -0.74]).

Significance: Here we show that, NKT and iNKT cells promote atherosclerosis. In general, NKT cell population increases with the progression of the plaque in mice and the numbers of iNKT cells reduce once the disease is established both in mice and humans.