Periodontitis is a disease caused by infection and immunological imbalance, which often leads to the destruction of periodontal tissue. Programmed death protein 1 (PD-1) and its ligand: programmed death ligand 1 (PD-L1) are important "immune checkpoint" proteins that have a negative regulatory effect on T cells and are targets of immunotherapy. Studies have shown that the expression of PD-1 and PD-L1 in patients with periodontitis is higher than that in healthy individuals. The keystone pathogen Porphyromonas gingivalis (P. gingivalis) is believed to be the main factor driving the upregulation of PD-1/PD-L1. High expression of PD-1/PD-L1 can inhibit the inflammatory response and reduce the destruction of periodontal supporting tissues, but conversely, it can promote the "immune escape" of P. gingivalis, thus magnifying infections. In addition, the PD-1/PD-L1 pathway is also associated with various diseases, such as cancer and Alzheimer's disease. In this review, we discuss the influence and mechanism of the PD-1/PD-L1 pathway as a "double-edged sword" affecting the occurrence and development of periodontitis, as well as its function in periodontitis-related systemic disorders. The PD-1/PD-L1 pathway could be a new avenue for periodontal and its related systemic disorders therapy.
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