NKG2D/ligands-mediated immune activation promotes atherosclerosis (142.7)

Abstract Atherosclerosis, a chronic vascular disease, is characterized by deposition of fatty substances and accumulation of immune cells in susceptible regions of arteries. Increasing evidence show that abnormal metabolic conditions, such as dyslipdemia and diabetes, induce immune cell activation and inflammation, which play crucial roles in progression of atherosclerosis. However, molecular linkers of metabolic disorder, immune activation and atherosclerosis are not well understood. Here we report that ligands for NKG2D, an immune-activating receptor, were upregulated in multiple tissues and organs under atherosclerotic disease condition, particularly in atherosclerotic lesion and liver. Preventing NKG2D/ligands interaction significantly reduced atherosclerotic lesion formation and systemic inflammation. In addition, preventing NKG2D/ligand interaction alleviated abnormal metabolic conditions by suppressing liver inflammation. Our data clearly show that NKG2D/ligand interaction plays critical roles in the progression of atherosclerosis and might be potential targets against atherosclerosis.