Inflammation is the immune response flooding a site of infection with immune cells. First observed and described by the Ancient Romans, inflammation has long been associated with disease. Scientists now recognize that inflammation is the body’s natural reaction to infection and helps control or the spread of pathogens. Acute inflammation is beneficial because it quickly identifies and eliminates the infection. However, chronic inflammation has been implicated in various diseases and is a critical hallmark for deadly pathologies, including cancer. During chronic inflammation immune cells are constantly signaling to continue an immune response. This can cause mutations and lead to toxic effects. Diseases associated with chronic inflammation include arthritis and autoimmune disorders, which are both on the rise.
Physicians try to mediate inflammation by prescribing medication, but that also limits immune response. Therefore, scientists are working to understand how to better target chronic inflammation, but still maintain effective immunity. A new study by researchers from Massachusetts General Brigham discovered a protein referred to as “WSTF” that could block chronic inflammation caused by aging and disease. Interestingly, this new target would not affect acute inflammation needed to control pathogens. This new target would allow the immune system to respond to short-term infections and prevent disease progression.
The study published in Nature, by Dr. Zhixun Dou and others, provides insight into the underlying mechanism of chronic inflammation. Dou is an independent investigator at the Center for Regenerative Medicine and Krantz Family Center for Cancer Research at Massachusetts General Hospital. His work focuses on mechanisms that promote aging and chronic illness. Specifically, his research group investigates cellular components that drive these processes of aging, which are also associated with deteriorating diseases such as cancer, heart disease, and neurodegeneration.
The research team used inflamed human cells and found WSTF prompts cells to excrete their nuclei. As a result, excreted nuclei expose pro-inflammatory genes, which are recognized by the body and amplify the immune response. Therefore, it is a positive feedback loop that continually generates chronic inflammation. Scientists were able to confirm that the loss of WSTF promotes inflammation in different mouse models of cancer. However, using inflamed human cells, showed the effect of WSTF loss only affected chronic inflammation, not acute. In an attempt to regulate this pathway, researchers developed a therapeutic that restored WSTF to reduce chronic inflammation but maintain acute immune responses. Preliminary experiments demonstrated efficacy of this therapeutic in various models representing aging, metabolic dysfunction-associated steatohepatitis (MASH), and osteoarthritis.
Scientists also found the loss of WSTF in patients with diseases associated with chronic inflammation, including MASH and osteoarthritis. Interestingly, by restoring WSTF, chronic inflammation is regulated. Further work needs to be conducted to confirm the efficacy and safety of restoring WSTF, but recent experiments suggest WSTF may hold the answer to mitigating chronic inflammation. Scientists are working on developing new strategies to target WSTF and improve quality of care in patients. Overall, the discovery of WSTF function offers a promising therapeutic target which can improve treatment efficacy and prolong patient longevity.
