Rheumatoid arthritis (RA) is an autoimmune, inflammatory disease. Though the precise mechanism of the disease is only partially understood, people with RA produce antibodies that target their own tissues, contributing to painful inflammation in the joints that can cause bone loss.
In a recent study published in the Journal of Clinical Investigation, researchers from Penn Dental Medicine found that the molecule DEL-1—already known to protect against periodontitis and other inflammatory diseases in animal models—similarly offers protection from the joint-damaging inflammation of RA. Using two distinct models of RA, the team, led by George Hajishengallis of Penn and Triantafyllos Chavakis of Germany's Technical University of Dresden, showed that DEL-1 acted in two ways: in the joints themselves, preventing immune cells from fostering inflammation, and in the lymph nodes, interfering with the production of joint-damaging antibodies.
"We find that DEL-1 has a dual action," says Hajishengallis, "both preventing the induction of autoantibodies, but also restraining the recruitment of inflammatory cells in the joints. I think that DEL-1 could be a very valuable therapeutic for rheumatoid arthritis, though we'll need support for clinical trials in humans to test this."
Hajishengallis' and Chavakis' labs have extensively studied DEL-1 for years in other inflammatory conditions, including periodontitis, a severe form of gum disease, and multiple sclerosis. They've shown that DEL-1 can restrain the initiation of inflammation and also resolve ongoing inflammation, depending on the context and location in which it is expressed.
Knowing that inflammation is the critical contributor to pathology in RA as well, they sought to test whether and how DEL-1 was at work in this new disease context.
Taken together with other previous work on DEL-1 and inflammatory conditions, the new findings lend support to the idea that DEL-1 itself could be a therapeutic in RA and perhaps other contexts, or that low DEL-1 levels could serve as a diagnostic for RA, a disease that is frequently a challenge to diagnose.
"The more genetic tools we have to investigate the role of DEL-1, the more we learn about how it is acting in these inflammatory conditions," Hajishengallis says. "We're hoping to capitalize on these discoveries in the future." Read more on the study >>
The work was supported by the National Institutes of Health (grants DE024153, DE029436, DE028561, and DE026152) and the German Research Foundation.
