PD-1/PD-L1 Axis as a Potential Therapeutic Target for Multiple Sclerosis: A T Cell Perspective.

Haixia Li,Chao Zheng,Jinming Han,Shan Liu,Jie Zhu,Tao Jin

doi:10.3389/fncel.2021.716747

Abstract

The programmed cell death protein-1/programmed death ligand-1 (PD-1/PD-L1) axis is a widely studied immune checkpoint that modulates signaling pathways related to T cell activation. The use of PD-1/PD-L1 inhibitors is a promising immune therapy strategy for cancer patients. However, individuals treated with PD-1/PD-L1 inhibitors may develop immune-related adverse events due to excessive immune reactions. Multiple sclerosis (MS) is a chronic demyelinating and neurodegenerative disease of the central nervous system. T cells and the PD-1/PD-L1 axis play vital roles in the pathogenesis of MS. A better understanding of the complex relationship between the PD-1/PD-L1 axis and T cells may extend our knowledge of the molecular mechanisms and therapeutic approaches for MS. In this review, we summarize the most recent findings regarding the role of the PD-1/PD-L1 axis in MS and discuss the potential therapeutic strategies to modulate the expression of PD-1/PD-L1 in MS.

Highlights

Multiple sclerosis (MS) is an autoimmune disease characterized by demyelination, axonal injury, and neuronal loss in the central nervous system (CNS), causing a variety of clinical symptoms involving motor, sensory, visual, and autonomic systems (Dobson and Giovannoni, 2019)
The regulatory effects of soluble PD-1 (sPD-1)/soluble PD-L1 (sPD-L1) in autoimmune diseases and tumors have been reported in previous studies (Table 1). They found that the expression of sPD-1/sPD-L1 was upregulated in patients with autoimmune diseases compared with healthy subjects, but downregulated after treatment, suggesting that sPD-1 may resist the inhibitory effect of membrane-bound PD1 on T cells, thereby indirectly enhancing immune responses
SPD-1 blocked the inhibitory effect of membrane-bound PD-1 on T cell activation, and induced the Th1/Th17 immune response sPD-1 aggravated the severity of rheumatoid arthritis (RA)

Summary

Introduction

Multiple sclerosis (MS) is an autoimmune disease characterized by demyelination, axonal injury, and neuronal loss in the central nervous system (CNS), causing a variety of clinical symptoms involving motor, sensory, visual, and autonomic systems (Dobson and Giovannoni, 2019). The activation of the PD-1 gene is involved in programmed cell death and can promote the evasion of tumor cells from effective immune responses. We propose that the activation of a variety of immune cells induces the production of proinflammatory cytokines during the relapsing phase of MS, and promotes the expression of PD1/PD-L1.

Results

Conclusion