Delicate Role of PD-L1/PD-1 Axis in Blood Vessel Inflammatory Diseases: Current Insight and Future Significance

Immune checkpoint molecules are the antigen-independent generator of secondary signals that aid in maintaining the homeostasis of the immune system. The programmed death ligand-1 (PD-L1)/PD-1 axis is one among the most extensively studied immune-inhibitory checkpoint molecules, which delivers a nega...

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Bibliographic Details
Published in:	International journal of molecular sciences 2020-10, Vol.21 (21), p.8159
Main Authors:	Veluswamy, Priya, Wacker, Max, Scherner, Maximilian, Wippermann, Jens
Format:	Article
Language:	eng
Subjects:	atherosclerosis and blood vessel inflammatory diseases B7-H1 Antigen - antagonists & inhibitors B7-H1 Antigen - immunology B7-H1 Antigen - metabolism coronary artery disease Humans Immune Checkpoint Inhibitors - therapeutic use PD-L1 PD-L2 Programmed Cell Death 1 Receptor - antagonists & inhibitors Programmed Cell Death 1 Receptor - immunology Programmed Cell Death 1 Receptor - metabolism programmed death-1 (PD-1) Review Vasculitis - drug therapy Vasculitis - immunology Vasculitis - metabolism Vasculitis - pathology
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Summary:	Immune checkpoint molecules are the antigen-independent generator of secondary signals that aid in maintaining the homeostasis of the immune system. The programmed death ligand-1 (PD-L1)/PD-1 axis is one among the most extensively studied immune-inhibitory checkpoint molecules, which delivers a negative signal for T cell activation by binding to the PD-1 receptor. The general attributes of PD-L1's immune-suppressive qualities and novel mechanisms on the barrier functions of vascular endothelium to regulate blood vessel-related inflammatory diseases are concisely reviewed. Though targeting the PD-1/PD-L1 axis has received immense recognition-the Nobel Prize in clinical oncology was awarded in the year 2018 for this discovery-the use of therapeutic modulating strategies for the PD-L1/PD-1 pathway in chronic inflammatory blood vessel diseases is still limited to experimental models. However, studies using clinical specimens that support the role of PD-1 and PD-L1 in patients with underlying atherosclerosis are also detailed. Of note, delicate balances in the expression levels of PD-L1 that are needed to preserve T cell immunity and to curtail acute as well as chronic infections in underlying blood vessel diseases are discussed. A significant link exists between altered lipid and glucose metabolism in different cells and the expression of PD-1/PD-L1 molecules, and its possible implications on vascular inflammation are justified. This review summarizes the most recent insights concerning the role of the PD-L1/PD-1 axis in vascular inflammation and, in addition, provides an overview exploring the novel therapeutic approaches and challenges of manipulating these immune checkpoint proteins, PD-1 and PD-L1, for suppressing blood vessel inflammation.
ISSN:	1422-0067 1661-6596 1422-0067