PD-L1 correlates with the presence of chemokines and cytokines in gingival crevicular fluid from healthy and diseased sites in smoking and non-smoking subjects with periodontitis

Periodontitis is an inflammatory disease of the supporting structures of the teeth that is caused by bacteria. Statistics show that approximately half of American adults over the age of 30 have some form of mild, moderate, or severe periodontitis and 70.1% of adults over the age of 65 have periodontitis. If left untreated, the long-term exposure to inflammation begins to destroy the soft tissues and tooth-supporting bone. If left unchecked, there can be enough destruction to result in tooth loss.

Early in the disease process, different bacterial populations on the surface of teeth begin to accumulate and form plaque. Plaque materials and the bacteria in them start to irritate normal tissues and induce early stages of inflammation. Irritated gum tissue begins to produce numerous chemical signals, called cytokines that attract immune cells to the site. Together, this process first begins to destroy the soft tissues and is characterized by increased amounts of fluid secretion in the gingiva (called gingival crevicular fluid or GCF), swelling and bleeding. Long-term chronic exposure to cytokines and immune cells can begin to erode underlying bone.

The immune reaction does not proliferate at an unchecked rate due to the production of regulatory ‘checkpoint’ molecules. Programmed Death-Ligand 1 (PD-L1) is an immune checkpoint molecule displayed on the surface of immune cells. Its presence and concentration regulates the balance between costimulatory and coinhibitory immune signals and maintains the breadth and magnitude of immune responses. It prevents adverse autoimmune inflammatory events and protects the host from uncontrolled immune responses to pathogens and inflammatory tissue damage.

This study a) assessed the production of PD-L1 in GCF and b) assessed the relationship of PD-L1 to other inflammatory cytokines previously detected in the same GCF. PD-L1 was found to be present in GCF, and these concentrations correlated with the presence of cytokines in GCF from healthy and diseased sites in smoking and non-smoking subjects with periodontitis. To what extent PD-L1 values contribute to the periodontal status of the site, smoking, and inflammatory tissue damage will have to be examined in future studies. Future research needs to fully characterize the presence and concentration of PD-L1 in periodontal tissues, the sites of PD-L1 production, the inducers of PD-L1 expression, and the role PD-L1 plays in the pathophysiology of periodontal disease, particularly in the expression of cytokine profiles. Future studies should also compare PD-L1 expression in subjects in a range of periodontal status including health, gingivitis and periodontitis.