Gum Cells Detect Shift in Mouth Microbes That May Trigger Inflammation, Gum Disease

In Brief:

• Aside from their role as a physical protective barrier, epithelial cells that line the mouth and gums (gingiva) may directly activate the immune system.
• Gingival epithelial cells, rather than immune cells, may be the harbingers of chronic inflammation that lead to gum disease.

Cells that line the mouth, gum (gingival) tissues, skin, lungs, and intestines, so-called epithelial cells, act as a physical barrier to protect the body from harmful substances in the environment. When a toxin, virus, or bacteria breaches this epithelial cell barrier, the immune system’s patrolling sentinel cells detect and ramp up an immune response to eradicate the threat.

However, NIDCR investigators have found new evidence in mice that an alternative scenario may be possible. Their findings suggest that epithelial cells in the gingiva, rather than patrolling immune cells, can detect potential harms and trigger an immune response by emitting a chemical beacon known as a cytokine. This immune response initiates inflammation that can become chronic, eventually leading to gingival disease. Gingival disease, also called gum or periodontal disease, can lead to loss of the tissue and bone that hold teeth in place. In the United States, it affects an estimated 47% of adults over age 30 and 70% of adults over age 65.

In the new study, published on March 20 in Immunity, the researchers discovered that when gingival epithelial cells detect a disruption in the mouth’s microbial community, they turn on a gene that makes the cytokine IL-23.

“While a little bit of inflammation can be a good thing, when IL-23 is involved, it’s bad news, because it switches inflammation from protective to pathogenic,” said NIDCR Associate Scientific Director and senior author of the study Niki Moutsopoulos, D.D.S., Ph.D.

Periodontal disease isn’t triggered by an infection per se, but by a change in the composition of the teeth’s microbes. Mobile bacterial species, which are present at minimal levels in a healthy microbiome, increase in periodontal disease and trigger inflammation.

In the new study, Dr. Moutsopoulos’ team demonstrated that removing epithelial cell receptors that detect parts of these potentially unhealthy bacteria eliminated IL-23’s harmful inflammatory response. In a separate experiment, mice bred to lack the gene that makes IL-23 everywhere but in the immune cells were protected from developing periodontal disease. Taken together, these results point to a role for epithelial cells in sensing harmful bacteria and orchestrating IL-23-induced inflammation that leads to periodontal disease.

The researchers said their findings reveal a mechanism for how periodontal disease develops in mice. Knowing the exact process by which periodontal disease develops means that researchers can now test new ways to prevent or treat it.

“We know IL-23 is implicated in conditions like Crohn’s disease in the intestine and psoriasis in the skin,” said Dr. Moutsopoulos. “However, we didn’t know if the epithelial cells in these organs instigate IL-23 production, as we’ve now shown in periodontal disease, or if this process is enabled only by the patrolling immune cells.”

To find out, the researchers scanned human epithelial cells from other locations in the body to determine if they also made IL-23. The team found low levels of IL-23 in healthy human epithelial tissue from the lungs, gastrointestinal tract, and skin, and much higher levels in cases of infection, cancer, and autoimmune disease in these same tissues. These findings suggest that epithelial cells may play a bigger role in disease development than previously appreciated.

“These seminal studies challenge current paradigms related to the underlying mechanisms that drive oral mucosal immunity and epithelial reactions to harmful pathogens. This study illuminates a potential mechanism for how periodontal disease is initiated and lays the framework for studies on other inflammatory diseases of the mucosal membranes that manifest clinically and affect the quality of life for so many. Such research will drive efforts to identify a common therapeutic target for these conditions,” said NIDCR Director Rena D’Souza, D.D.S., Ph.D., M.S.

Related Links:

• Probing Periodontal Disease
• The Gut’s Role in Oral Bone Health
• Disarming a Blood-Clotting Protein Prevents Gum Disease in Mice

Reference:

Kim TS, Ikeuchi T, Theofilou VI, Williams DW, Greenwell-Wild T, June A, et al. Epithelial-derived interleukin-23 promotes oral mucosal immunopathology. Immunity. 2024 Mar 19:S1074-7613(24)00096-7. doi: 10.1016/j.immuni.2024.02.020.

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