In an effort to train the innate immune system to fight inflammatory diseases such as periodontitis and arthritis, researchers at the University of Pennsylvania School of Dental Medicine, in collaboration with the Technische Universität Dresden, have found that the process leads to increased bone loss in mice.
The study, published in ScienceDirect, explores the concept of “trained immunity,” also known as TRIM, in which the innate immune system responds more strongly to repeated or similar stimuli. This phenomenon challenges the long-held notion that only the adaptive immune system has similar memory abilities.
“The body also has an innate immune branch that has long been considered merely the first-line and general attack arm of the immune system, without the ability to remember previous attacks or to respond differently if challenged again,” Penn’s School of Dental Medicine said in a press release Thursday.
To induce trained immunity in their experimental models, the research team used beta-glucan, a compound found in certain fungi. They then measured the activity of osteoclasts, cells responsible for bone resorption, in mouse models of periodontitis and arthritis. The researchers found that while beta-glucan itself does not cause bone loss, it increases the likelihood of bone deterioration in the presence of secondary inflammatory stimuli, such as arthritis or periodontal disease.
“This requirement embodies the concept of ‘trained immunity’ – a training stimulus primes the organism for future events,” said George Hajishengallis, the Thomas W. Evans Centennial Professor in the Department of Basic and Translational Sciences at the University of Pennsylvania School of Dental Medicine. “The double-edged sword of TRIM has particular implications for the preventive or therapeutic application of TRIM inducers.”
The authors concluded that their findings “establish trained osteoclastogenesis as a maladaptive component of TRIM and may provide a therapeutic target for inflammatory osteoporosis.”
Scientists are increasingly exploring the potential of the immune system to treat disease through both its adaptive and innate branches. Earlier this year, Australian researchers published in the journal Science Immunology that they had discovered a class of stem-like T cells with enhanced regenerative capacity that could be promising targets for cancer immunotherapy. These T cells are regulated by the transcription factor ID3 and have been shown to sustain CD8 T cell responses in chronic infection and tumor settings.
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