T cells help fight off infection, but they can go overboard. A study published today in Science Translational Medicine shows that a subset of T cells, Th17 cells, contributes to the inflammation and bone loss that is associated with periodontitis—a severe form of gum disease. The research presents a new target for treating periodontitis and other diseases involving the inappropriate response of Th17 cells, including autoimmune conditions such as rheumatoid arthritis and multiple sclerosis.
The researchers looked at gum tissue from patients with chronic periodontitis and confirmed that they had higher numbers of Th17 cells compared to healthy controls. They also observed that when they induced periodontitis in mice, the number of Th17 cells and the IL-17 signaling molecule that they produce increased with the onset of gum disease. The increase was the result of local proliferation rather than recruitment from nearby lymph nodes.
To interrogate possible triggers of the local expansion of Th17 cells, the team looked into how changes in the microbial community in the gums affected the accumulation of Th17 cells. In the mouse model of disease, animals were treated with broad- or narrow-spectrum antibiotics. Only the antibiotics that lowered the numbers of Th17 cells were capable of suppressing the disease.
Finally, the researchers looked at a mouse model missing a key protein required for Th17 cell development and a group of human patients with a mutation in the corresponding gene—Stat3. In both cases, they found that the Stat3 mutation, which dramatically cut the number of Th17 cells present in the gum tissue, also protected against the bone loss seen in chronic periodontitis. While people with this Stat3 mutation have other problems, gum disease is not one of them.
"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," says George Hajishengallis of the University of Pennsylvania. "This type of rigorous evidence is not easy to come by in medical science."
Though antibiotics could protect against the disease, the side effects would be too significant to justify the treatment. But employing a small-molecule that inhibits Th17 cell development gave the researchers a similar effect, reducing Th17 cell accumulation and associated periodontal bone loss in mice.