13 March 2026

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Discovery Reveals How Diabetes Worsens Periodontal Disease

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Researchers at Penn Dental Medicine have identified an important immune signaling pathway through which diabetes exacerbates periodontal disease.

Periodontal disease, one of the most common human diseases, affects well over half of older adults in the United States. Driven by an imbalance in the natural bacterial population in the mouth, it causes chronic inflammation in gum tissue, and ultimately the loss of the supporting jawbone and teeth if it progresses. Periodontal disease tends to be much worse in people who have diabetes, another very common disease. In the study, published in the Journal of Clinical Investigation, the Penn Dental researchers used animal models, analyses of human gum tissue, and other techniques to illuminate how diabetes caused changes that increased tissue destruction.

“We’ve known that diabetes increases both the risk and the severity of periodontal disease, largely through increased inflammation, and here we’ve taken the next step and identified a major signaling pathway driving that increased inflammation,” said the study’s senior author Dana Graves, DDS, DMSc, professor and interim chair of the Department of Periodontics and Vice Dean for Scholarship and Research at Penn Dental Medicine.

Using a well-established mouse model of periodontal disease, the researchers linked diabetes-worsened inflammation and bone loss to increased numbers of a T cell type that secretes the pro-inflammatory protein IL17A, and also noted a reduced population of immune-damping T cells called Treg cells.

Ultimately, they found that this effect depended on a signaling interaction between the protein CD137L, which is expressed on the surface of cells that activate the immune response called dendritic cells, and its matching receptor, CD137, on T cells that carry out the immune response. The CD137L-CD137 pathway is known as a pro-inflammatory enhancer of T cell activity that has been studied in cancer biology. The experiments shed light on why this pathway is linked to diabetes, showing that dendritic cells express CD137L at higher levels in a high-glucose, diabetic environment.

The findings also suggested that activity of the CD137L-CD137 pathway in diabetes is not limited to mice: In a group of periodontal disease patients examined by the researchers, dendritic cells in affected gum tissue were twice as likely to express CD137L when the patients had high blood glucose levels, compared to patients with normal blood glucose.

The good news was that by inhibiting CD137L in dendritic cells, the mice had greatly reduced diabetes-enhanced periodontal inflammation and bone loss—implying that CD137L, or factors that govern its production in dendritic cells, could be a therapeutic target.

The findings represent a step forward in understanding how diabetes worsens inflammation, and highlights the involvement of T cells in the inflammatory response to bacteria.

Source: https://www.dental.upenn.edu/