Abstract
Immune responses in the central nervous system (CNS), which involve both resident glial cells and infiltrating peripheral immune cells, play critical roles in the progress of brain injuries and neurodegeneration. To avoid inflammatory damage to the compromised brain, the immune cell activities in the CNS are controlled by a plethora of chemical mediators and signal transduction cascades, such as inhibitory signaling through programed death-1 (PD-1) and programed death ligand (PD-L) interactions. An increasing number of recent studies have highlighted the importance of PD-1/PD-L pathway in immune regulation in CNS disorders such as ischemic stroke, multiple sclerosis, and Alzheimer’s disease. Here, we review the current knowledge of the impact of PD-1/PD-L signaling on brain injury and neurodegeneration. An improved understanding of the function of PD-1/PD-L in the cross-talk between peripheral immune cells, CNS glial cells, and non-immune CNS cells is expected to shed further light on immunomodulation and help develop effective and safe immunotherapies for CNS disorders.
Highlights
The central nervous system (CNS) was traditionally thought to tolerate the invasion of antigens without an inflammatory response
The expression of programed death-1 (PD-1) and programed death ligand (PD-L) on many immune and nonimmune cells surely allows for multiple tiers of immunoregulation in the CNS and remains an active area of investigation
Given the complexity of inflammatory responses in the CNS, our current understanding of the function of PD-1/PDL in the cross-talk between peripheral immune cells, CNS glial cells, and non-immune CNS cells still lies in its infancy
Summary
Reviewed by: Vikramjeet Singh, LudwigMaximilians-Universität, Germany Halina Offner, Oregon Health & Science University, USA. Immune responses in the central nervous system (CNS), which involve both resident glial cells and infiltrating peripheral immune cells, play critical roles in the progress of brain injuries and neurodegeneration. An increasing number of recent studies have highlighted the importance of PD-1/PD-L pathway in immune regulation in CNS disorders such as ischemic stroke, multiple sclerosis, and Alzheimer’s disease. We review the current knowledge of the impact of PD-1/PD-L signaling on brain injury and neurodegeneration. An improved understanding of the function of PD-1/PD-L in the cross-talk between peripheral immune cells, CNS glial cells, and non-immune CNS cells is expected to shed further light on immunomodulation and help develop effective and safe immunotherapies for CNS disorders
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