In research intended to shed light on the inflammatory stress response that triggers the development of rheumatoid arthritis, US scientists have discovered a specific IRE1a inhibitor that can counter the condition in animal models.
The study, entitled “Toll-like receptor-mediated IRE1a activation as a therapeutic target for inflammatory arthritis” and published in the journal EMBO, is the joint work of researchers from the Northwestern University Feinberg School of Medicine and Wayne State University´s School of Medicine. The researchers discovered that inflammatory stimuli activate toll-like receptors of macrophages (the white blood cells within tissues) on the cell surface, which subsequently trigger the Unfolded Protein Response (UPR) transducer IRE1a to inflame the tissues around the joints.
The findings are key to understanding the stress mechanism for the development of rheumatoid arthritis, said Kezhong Zhang, associate professor of immunology and microbiology. This is the first time that the molecular targets of UPR and toll-like receptor signalling have been identified and also the first study to show their interaction in the development of inflammatory arthritis and discover a specific inhibitor that can tackle its progression, he added.
According to Zhang, the next move towards the discovery of therapeutics for the disease could be examining the effects of specific inhibitors of UPR in curing inflammatory arthritis in animal models and clinical studies.
Rheumatoid arthritis is an autoimmune disease that is accompanied by inflammation, pain and swelling of joints. The condition affects many tissues and organs, but mainly attacks flexible joints.