A Royal Melbourne Hospital researcher at the Walter and Eliza Hall Institute has helped reveal new details about how joint inflammation evolves in rheumatoid arthritis, and the cells that prolong the inflammatory attack.
Published in the Journal of Experimental Medicine, the team detailed how immune cells called natural killer (NK) cells are an unexpected source of the inflammatory protein GM-CSF in rheumatoid arthritis, and is the first clue in how these cells contribute to inflammatory autoimmune diseases.
The study also looked at how GM-CSF signals to other immune cells to prolong joint inflammation, and how GM-CSF signalling to immune cells is kept in check in healthy joints. The team identified the protein CIS as a key molecular “brake” that dampens GM-CSF activity and inflammation.
The research was completed by a team at WEHI co-led by the Royal Melbourne Hospital’s Professor Ian Wicks and Monash University’s Professor Nicholas Huntington.
The Royal Melbourne Hospital’s Professor Wicks said that these discoveries could lead to potential new therapeutic targets for reducing joint inflammation in rheumatoid arthritis, and other inflammatory diseases such as multiple sclerosis.
“Our earlier research, together with Professor John Hamilton at the University of Melbourne, identified the signalling protein GM-CSF as an important contributor to joint inflammation in rheumatoid arthritis, but which cells were producing GM-CSF within inflamed joints, and how this protein signalled after binding to its receptor on other immune cells, was not well understood,” Professor Wicks said.
“When we discovered that GM-CSF in inflamed arthritis joints was produced by NK cells, this was a surprise,” one of the study’s authors, WEHI scientist Dr Cynthia Louis said, “because, until now, NK cells were thought to primarily be important for clearing virus-infected or cancer cells,”
“This is the first time NK cells have been found to contribute to tissue inflammation in autoimmune diseases such as rheumatoid arthritis,” she said.
Dr Louis said that the discovery “has solved one part of the puzzle” in rheumatoid arthritis, a condition that affects over 250,000 Australians.
In addition to the discovery of GM-CSF as a contributor of inflammation in rheumatoid arthritis, the team also found that the protein CIS is able to “switch off” GM-CSF signalling.
“This research showed that if a new drug that mimics CIS were to be developed, it may help to reduce the debilitating effects of GM-CSF in rheumatoid arthritis, but also in other inflammatory diseases driven by GMCSF, such as multiple sclerosis.”
Professor Wicks said the research revealed new aspects of cell signalling that warranted further investigation.
“We’re very excited to have progressed our understanding of rheumatoid arthritis and potentially other inflammatory diseases,” he said.