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Updated: Aug 13, 2025

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Published on: June 3, 2018
The Programmed Death-1 Signaling Axis Modulates Inflammation and LV Structure/Function in a Stress-Induced
Tomohiro Hayashi1, Sajal K Tiwary1, Kory J Lavine1
1Center for Cardiovascular Research, Cardiovascular Division, Department of Medicine, Washington University School of Medicine, St Louis, Missouri, USA.
Abstract:
The role of immune checkpoints in the setting of tissue injury remains unknown. Using an experimental model of isoproterenol (ISO)-induced stress cardiomyopathy, we show that ISO-induced myocardial injury provokes tissue-autonomous up-regulation of the programmed death-1 (PD-1):programmed death ligand (PD-L) axis in cardiac resident innate immune cells and T cells. PD-1 signaling was responsible for modulating the acute inflammatory response, as well as normalization of impaired left ventricular structure and function after ISO injection. Necrotic cardiac extracts were sufficient to increase the expression of PD-1 in macrophages and T cells in vitro. Viewed together these studies suggest that the PD-1:PD-L signaling axis regulates immune responses to cardiac tissue injury and is important for restoring myocardial homeostasis.
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