Death of macrophages, an immune cell type, can trigger rheumatoid arthritis, researchers suggest, adding that the protein A20 could prevent macrophage death and protect against the disease.
These findings open up new possibilities for the treatment of this disease, according to research groups from the University of Cologne, VIB, Ghent University, the Βiomedical Sciences Research Center ‘Alexander Fleming’ in Athens and the University of Tokyo.
Their study was published recently in Nature Cell Biology.
The study — a collaboration between Prof Manolis Pasparakis and Dr Apostolos Polykratis (University of Cologne), Dr Marietta Armaka (BSRC ‘Alexander Fleming’, Athens), Dr Yoshitaka Shirasaki and Dr Yoshifumi Yamaguchi (University of Tokyo), and Prof Geert van Loo and Arne Martens (VIB-UGent) — builds further upon earlier research at the VIB-UGent Center for Inflammation Research, which demonstrated that the protein A20 suppressed arthritis by preventing inflammation.
Now the researchers show that the inflammatory response is caused by the fact that a fraction of specialized immune cells, macrophages, die by a specific inflammation-promoting type of cell death called necroptosis. The researchers were able to prevent the development of RA by blocking necroptosis, a media release from VIB (the Flanders Institute for Biotechnology) explains.
“We could also identify why these macrophages are dying and could demonstrate the importance of a specific part in the protein A20 for the prevention of cell death and RA development,” van Loo says.
“We revealed how the particular type of macrophage demise shapes the activation of synovial fibroblasts, a key cell type that orchestrates the destruction of cartilage and bone tissue in RA,” Armaka adds.
This study confirms the crucial importance of A20 in the control of inflammation, but now also shows that preventing cell death is a critical anti-inflammatory function of A20 to protect against arthritis, the researchers suggest.
“From a therapeutic perspective, this is a very important finding, since it suggests that drugs inhibiting cell death could be effective in the treatment of RA, at least in a subset of patients where macrophage death could provide the underlying trigger,” Pasparakis states.
Several pharmaceutical companies are developing new drugs to inhibit cell death, which will hopefully help to treat patients suffering from inflammatory diseases, including rheumatoid arthritis, the release concludes.
[Source(s): VIB (the Flanders Institute for Biotechnology), EurekAlert]
