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Review
. 2023 May 16:14:1163633.
doi: 10.3389/fimmu.2023.1163633. eCollection 2023.

The role of PD-1 signaling in health and immune-related diseases

Ru-Yue Chen  1 , Yun Zhu  1 , Yun-Yan Shen  1 , Qin-Ying Xu  1 , Han-Yun Tang  1 , Ning-Xun Cui  1 , Lu Jiang  1 , Xiao-Mei Dai  1 , Wei-Qing Chen  1 , Qiang Lin  1 , Xiao-Zhong Li  1
Affiliations
Review

The role of PD-1 signaling in health and immune-related diseases

Ru-Yue Chen et al. Front Immunol. .

Abstract

Programmed cell death 1 receptor (PD-1) and its ligands constitute an inhibitory pathway to mediate the mechanism of immune tolerance and provide immune homeostasis. Significantly, the binding partners of PD-1 and its associated ligands are diverse, which facilitates immunosuppression in cooperation with other immune checkpoint proteins. Accumulating evidence has demonstrated the important immunosuppressive role of the PD-1 axis in the tumor microenvironment and in autoimmune diseases. In addition, PD-1 blockades have been approved to treat various cancers, including solid tumors and hematological malignancies. Here, we provide a comprehensive review of the PD-1 pathway, focusing on the structure and expression of PD-1, programmed cell death 1 ligand 1 (PD-L1), and programmed cell death 1 ligand 2 (PD-L2); the diverse biological functions of PD-1 signaling in health and immune-related diseases (including tumor immunity, autoimmunity, infectious immunity, transplantation immunity, allergy and immune privilege); and immune-related adverse events related to PD-1 and PD-L1 inhibitors.

Keywords: autoimmune diseases; immune checkpoint proteins; immune tolerance; immunotherapy; programmed cell death 1 receptor; tumor microenvironment.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Involvement of PD-1 signaling in health and immune-related diseases.
Figure 2
Figure 2
Mechanisms of PD-1-mediated inhibition in T cells. After interacting with PD-L1 or PD-L2, PD-1 recruits the phosphatase SHP-2 in proximity to TCR, which attenuates key TCR proximal signaling, including the PI3K-PDK1-AKT-mTOR pathway and the RAS-RAF-MEK-ERK pathway.
Figure 3
Figure 3
The diverse binding partners of PD-1 and its associated ligands.
See this image and copyright information in PMC

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