Researchers from Penn’s School of Dental Medicine discovered that training the innate immune system may lead to increased bone loss in inflammatory conditions such as periodontitis and arthritis.
Published in Developmental Cell, the study involved international collaborators from both the Dresden University of Technology and Penn investigating the effects of innate immune system training in experimental models of inflammatory bone loss.
This focus on innate immunity is a different approach to studying immunity. Past approaches were largely focused on the adaptive immune system — which is able to identify previous infections and respond to them accordingly once re-encountered — while the innate immune system was simply treated as the first line of defense, unable to “remember” past infections in the same manner as the adaptive immune system.
“If you go and look at an immunology textbook — even today — it will likely tell you that innate immunity has no memory,” George Hajishengallis, Thomas W. Evans Centennial Professor in the Department of Basic & Translational Sciences at Penn Dental Medicine, told Penn Today.
However, recent research has challenged this belief, showing that the innate immune system can be trained. This emerging principle, known as trained innate immunity, enables the innate immune system to respond more robustly when exposed to a repeat or even different stimulus. Researchers in this study explored how this training affects osteoclastogenesis — a process in which osteoclasts, or specialized cells, break down bone.
“We found that this treatment primed osteoclast precursors to differentiate into osteoclasts more readily if presented with an inflammatory challenge like arthritis,” Triantafyllos Chavakis, W3-Professor and Director of the Institute for Clinical Chemistry at the Dresden University of Technology, said.
Utilizing beta-glucan, a compound found in certain fungi, the researchers measured osteoclasts during TRIM. The discovery suggested that TRIM could be associated with inflammatory disease; however, it also distinguished that beta-glucan did not directly lead to bone loss in the absence of a second inflammatory stimulus, but rather increased its chances.
“This requirement for a secondary challenge epitomizes the concept of trained immunity,” Hajishengallis said. “The training stimulus causes a state of preparedness for future events.”
While previous studies have shown that TRIM can enhance immune responses against infections and even cancer, the Penn study underscores its potential to contribute to inflammatory diseases. Given these implications, the researchers emphasized the importance of understanding the context in which TRIM emerges.
“A better understanding of TRIM is imperative to appropriately harness it for therapeutic gain in human disease,” Hajishengallis added.
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