Dual role played by NKT cells in the development of atherosclerosis: Evidence from meta-analysis of pre-clinical studies

Abstract

Background and Aims : NKT cells play crucial role in regulating early inflammation in atherosclerosis. Broadly, there are two subsets, invariant (iNKT) and variant (vNKT), where iNKTs are thought to be pro-atherosclerotic, yet uncertainty remains.Methods: We performed a pre-clinical meta-analysis to understand the true role of NKT cells in atherosclerosis. Twenty studies comprising 550 mice were selected for the meta-analysis. A random-effect model was employed to estimate the effect size. Additionally, we also fed high-fat-diet (HFD) to ApoE-null mice for 5 weeks, followed by identification of NKT lymphocytes from liver, spleen and blood with antibodies and α-GalCer loaded CD1d tetramer and flow cytometric analysis.Conclusions: This is the first meta-analysis on NKT cells and its subsets in preclinical atherosclerotic models. Based on this analysis and our data, we conclude that both NKT and iNKT cells are pro-atherosclerotic in nature, however, a gap still remains in the understanding of interplay of both subsets of NKT cells in atherosclerosis. Background and Aims : NKT cells play crucial role in regulating early inflammation in atherosclerosis. Broadly, there are two subsets, invariant (iNKT) and variant (vNKT), where iNKTs are thought to be pro-atherosclerotic, yet uncertainty remains. Methods: We performed a pre-clinical meta-analysis to understand the true role of NKT cells in atherosclerosis. Twenty studies comprising 550 mice were selected for the meta-analysis. A random-effect model was employed to estimate the effect size. Additionally, we also fed high-fat-diet (HFD) to ApoE-null mice for 5 weeks, followed by identification of NKT lymphocytes from liver, spleen and blood with antibodies and α-GalCer loaded CD1d tetramer and flow cytometric analysis. Conclusions: This is the first meta-analysis on NKT cells and its subsets in preclinical atherosclerotic models. Based on this analysis and our data, we conclude that both NKT and iNKT cells are pro-atherosclerotic in nature, however, a gap still remains in the understanding of interplay of both subsets of NKT cells in atherosclerosis.