Penn Dental Medicine Study Shows Innate Immune Training Aggravates Inflammatory Bone Loss

PHILADELPHIA, May 1, 2025 /PRNewswire/ -- Clinical research has long focused on ways to harness the actions of the immune system. From vaccines to immunotherapies, researchers have used their knowledge of the immune system to develop therapies to treat or prevent diseases from influenza to autoimmune disease and cancer.

Now, researchers from Penn Dental Medicine and international collaborators have investigated the effects of training the innate immune system in experimental models of two inflammatory diseases: periodontitis and arthritis. They find that this "trained" immunity, or TRIM, leads to increased bone loss in these models. This study is published in Developmental Cell.

Previous approaches have largely focused on the adaptive immune system, that branch of the immune system that "remembers" previous threats and launches specific attacks when it encounters them again. The body also has an innate immunity branch, which, for a long time, was just considered the first-line, general attack arm of the immune system with no ability to remember prior assaults or respond differently when rechallenged.

This belief has been challenged over the past decade, notes George Hajishengallis the Thomas W. Evans Centennial Professor in the Department of Basic & Translational Sciences at Penn Dental Medicine. Studies have shown that the innate immune system can respond more strongly when challenged again with the same or different stimulus—in other words, it can be "trained."

These studies have also shown that "training" the innate immune system can have beneficial effects, such as anti-tumor activity and an increased response to fighting infections. But inflammation—the innate immune system's natural response to harmful stimuli—can also exacerbate symptoms or even cause diseases, demonstrating the need to better understand the immune system when developing immune-based therapies.

The Hajishengallis team in collaboration with Dresden University of Technology induced TRIM using ß-glucan, a compound found in certain fungi, and measured the generation of osteoclasts, which resorb bone during growth and healing, in models of inflammatory periodontitis and arthritis.

Their work showed that ß-glucan increases the opportunity for bone loss to occur but does not cause actual bone loss. That only occurs if a second inflammatory stimulus, such as arthritis or periodontitis, is present.

"This requirement epitomizes the concept of trained immunity—the training stimulus causes a state of preparedness for future events," says Hajishengallis. "The double-edged sword of TRIM acquires special relevance for the preventive or therapeutic application of TRIM-inducing agents."

Media Contact: Beth Adams, [email protected]

SOURCE PENN DENTAL MEDICINE