Study identifies pathway linked to rheumatoid arthritis

November 11, 2015

"When we looked at macrophages from patients with arthritis, we found that the whole inhibitory pathway would not work," Dr. Ivashkiv said. "What this study suggests is that one of the things that contributes to inflammation in arthritis is crippling of beneficial pathways that usually serve to turn inflammation off." He said clinicians in the future may be able to focus on therapies that will augment or reinstitute these beneficial or homeostatic pathways as a way of turning off inflammation in chronic arthritis.

"Before this study we knew that ITAM-coupled receptors had the potential to inhibit inflammatory cytokine production, but there was very limited knowledge about how that worked," Dr. Ivashkiv said. "What we accomplished with the study is that we have increased our understanding of an indirect inhibitory mechanism that we think can serve as the basis for designing new approaches to therapy. This work implicates for the first time a negative role for calcium signaling downstream of these ITAM-coupled receptors and explains how that works,"

He added that investigators believe that there is extensive crosstalk among the various pathways and they think that the ITAM receptors play a very important role in deciding how all the signaling gets integrated. "In terms of the homeostatic pathways that control inflammation, we think that this pathway that we have described is one of the strongest ones. It completely turns things off," Dr. Ivashkiv said. "What you usually see are these partial inhibitions or attenuations in terms of inflammatory cytokine production. What we saw was a complete inhibition of the response."

Dr. Ivashkiv said future work would focus on further elucidating molecular details of the pathway and further testing of its importance in arthritis and animal models of disease.

SOURCE Hospital for Special Surgery

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