New Discovery: A Pathway That Can Stop Inflammation in Rheumatoid Arthritis

HSS scientists and rheumatologists have pinpointed a cellular pathway that can halt the painful and destructive inflammatory response of the immune system gone awry in rheumatoid arthritis. It's the immunoreceptor tyrosine-based activation motif coupled receptor – or ITAM pathway.

"It completely turns things off," reports Lionel Ivashkiv, MD, Associate Chief Scientific Officer and David H. Koch Chair in Arthritis and Tissue Degeneration, who led the multi-center study. "What we saw was the ITAM pathway triggering a complete inhibition of the inflammatory response. In the 20 years or so I have been studying regulation of inflammation, this seems to be the most potent inhibitory mechanism we have ever seen."

Until now, the ITAM pathway had never been established – or even studied – as specifically involved in rheumatoid arthritis. But it had been shown to suppress so-called Toll-like receptors on pathways that promote inflammation. The team thought perhaps a secondary pathway might be involved.

That second pathway (DAP12-Syk-Pyk2-p38-MSK) was found and with it a first-time role for calcium signaling downstream of the ITAM activated receptors. The team speculates the ITAM pathway helps integrate the extensive cross-talk that must necessarily happen among the cytokines of the many pathways involved in inflammation.

Discovering exactly how the ITAM pathway can so fully stop the inflammatory process will be the team's next focus. Aiming, as Dr. Ivashkiv notes, "To develop new treatments that can harness or control the ITAM pathway's natural ability to stop inflammation completely. Ultimately bringing freedom from pain due to inflammation to arthritis sufferers everywhere."


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