Th17 Immune Cells Drive Bone Loss in Periodontitis

Dentistry Today
Credit: NIDCR


Credit: NIDCR

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, according to researchers at the National Institute of Dental and Craniofacial Research (NIDCR) and the University of Pennsylvania School of Dental Medicine who say their findings have implications for new treatment approaches for the condition.

“We’ve known for years that microbes stimulate inflammation. Removing bacteria by tooth-brushing and dental care controls inflammation, but not permanently, suggesting there are other factors at play,” said NIDCR clinical investigator and senior author Niki Moutsopoulos, DDS, PhD. “Our results suggest that immune cells known as T helper 17 (Th17) cells are drivers of this process, providing the link between oral bacteria and inflammation.”

“I think this work leaves no doubt that these cells are important mediators of periodontitis,” said George Hajishengallis, DDS, PhD, the Thomas W. Evans Centennial Professor in the Department of Microbiology at Penn Dental Medicine. “The translational aspect of our studies is pinpointing a new approach to blocking the tissue destruction we see in periodontitis by inhibiting Th17 development.”

Th17 cells normally live in barrier sites such as the mouth, skin, and digestive tract where germs first make contact with the body. They protect against oral thrush but are also linked to psoriasis, colitis, and other inflammatory diseases, suggesting they play dual roles in health in disease.

In the study, these cells were much more prevalent in the gum tissue of humans with periodontitis than in the gums of their healthy counterparts. Also, the amount of Th17 cells correlated with disease severity. Similarly, more Th17 cells accumulated in the gums of mice with periodontitis compared to healthy mice, which served as a control group.

To see if the oral microbiome might be the trigger for Th17 cell accumulation, 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 that an unhealthy bacterial population triggers Th17 cell accumulation. 

To see if blocking Th17 cells could reduce periodontal disease, the researchers genetically engineered mice to lack Th17 cells or gave the animals a small-molecule drug that prevents Th17 cell development, finding 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 35 patients at the National Institutes of Health Clinical Center with a gene defect causing them to lack Th17 cells. The researchers reasoned that if Th17 cells are as important to periodontitis as the animal studies suggested, a lack of Th17 cells should protect against gum disease. The researchers, then, found that these patients were less susceptible to the condition and had less inflammation and bone loss compared to age-matched and gender-matched volunteers.

“Here we have a unique patient population with the same defect we checked in the mice, and they are similarly not susceptible to the same disease,” Hajishengallis said. “This type of rigorous evidence is not easy to come by in medical science.”

“Our clinical observations point to the relevance of our animal studies to humans and provide further evidence that Th17 cells are drivers of periodontitis,” said NIDCR researcher and first author Nicolas Dutzan, PhD.

“These results provide key insights into the mechanisms that underlie development of periodontal disease,” said NIDCR director Martha J. Somerman, DDS, PhD. “Importantly, they also offer compelling evidence for therapeutic targeting of specific cells, which might eventually help us provide better treatment and more relief to patients with this common disease.”

The study, “A Dysbiotic Microbiome Triggers TH17 Cells to Mediate Oral Mucosal Immunopathology in Mice and Humans,” was published by Science Translational Medicine.

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