Researchers identify immune culprits linked to inflammation and bone loss in gum disease

An unhealthy population of microbes in the mouth triggers specialized immune cells that inflame and destroy tissues, leading to the type of bone loss associated with a severe form of gum disease.

Periodontal disease is driven by Th17 immune cells, which are triggered by an unhealthy bacterial community. Photo: NIDCR

Periodontal disease is a common disorder. In those affected, bacteria trigger inflammation of the tissues that surround the teeth, which can lead to loss of bone and teeth in an advanced stage of the disease called periodontitis.

The research from the National Institute of Dental and Craniofacial Research (NIDCR) and the University of Pennsylvania School of Dental Medicine, Philadelphia, observed that T helper (Th) 17 cells were much more prevalent in the gum tissue of humans with periodontitis than in the gums of their healthy counterparts, and that the amount of Th17 cells correlated with disease severity.

Th17 cells normally live in so-called barrier sites—such as the mouth, skin, and digestive tract—where germs make first contact with the body.

Th17 cells are known to protect against oral thrush, a fungal infection of the mouth, but they are also linked to inflammatory diseases such as psoriasis and colitis, suggesting that they play dual roles in health and disease.

The scientists found that similar to humans, more Th17 cells accumulated in the gums of mice with periodontitis compared to healthy mice, which served as a control group.

The researchers placed mice on a broad-spectrum antibiotic cocktail. They found that eliminating oral microbes prevented expansion of Th17 cells in the gums of mice with periodontitis while leaving other immune cells unaffected, suggesting an unhealthy bacterial population triggers Th17 cell accumulation.

When the scientists genetically engineered mice to lack Th17 cells, or gave the animals a small-molecule drug that prevents Th17 cell development, they saw similar outcomes: reduced bone loss from periodontitis.

RNA analysis showed the Th17-blocking drug led to reduced expression of genes involved in inflammation, tissue destruction, and bone loss, suggesting that Th17 cells may mediate these processes in periodontitis.

Finally, the researchers studied a group of patients with a gene defect causing them to lack Th17 cells. The scientists reasoned that if Th17 cells are as important to periodontitis as the animal studies suggested, not having Th17 cells should protect against gum disease.

This is indeed what the group found—the patients were less susceptible to the condition and had less inflammation and bone loss compared to age- and gender-matched volunteers. (National Institutes of Health)

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