Year: 2017
Type: article
Abstract: Patients with coronary artery disease (CAD) are at high risk for reactivation of the varicella zoster virus (VZV) and development of herpes zoster (HZ). Here, we found that macrophages from patients with CAD actively suppress T cell activation and expansion, leading to defective VZV-specific T cell immunity. Monocyte-derived and plaque-infiltrating macrophages from patients with CAD spontaneously expressed high surface density of the immunoinhibitory ligand programmed death ligand-1 (PD-L1), thereby providing negative signals to programmed death-1+ (PD-1+) T cells. We determined that aberrant PD-L1 expression in patient-derived macrophages was metabolically controlled. Oversupply of the glycolytic intermediate pyruvate in mitochondria from CAD macrophages promoted expression of PD-L1 via induction of the bone morphogenetic protein 4/phosphorylated SMAD1/5/IFN regulatory factor 1 (BMP4/p-SMAD1/5/IRF1) signaling pathway. Thus, CAD macrophages respond to nutrient excess by activating the immunoinhibitory PD-1/PD-L1 checkpoint, leading to impaired T cell immunity. This finding indicates that metabolite-based immunotherapy may be a potential strategy for restoring adaptive immunity in CAD.
DOI: 10.1172/jci92167
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: G1556766700, G1588279094, Immunity, Inflammation and Hypertension, G1809139246, G3119200932, G366100091, Oligoclonal T Cell Expansion and Rheumatoid Arthritis, G6241365711, FAS ANTIGEN AND LIGAND--FUNCTIONAL CHARACTERIZATION, G7126395394, G8176476595, G9000017482, G9000060880, G9000110302, G9000123093, G9000126294, G9000150726, G9000222606, G9000269492, The NOTCH Signaling Pathway in Large Vessel Vasculitis
OpenAlex ID: W2623710583