Open AccessActivation of formyl peptide receptor 1 elicits therapeutic effects against collagen‐induced arthritis
Author(s) -
Park Byunghyun,
Lee Mingyu,
Kim Sang Doo,
Jeong Yu Sun,
Kim Ji Cheol,
Yang Siyoung,
Kim Hye Young,
Bae YoeSik
Publication year - 2021
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.16854
Subject(s) - inflammation , rheumatoid arthritis , arthritis , agonist , autoantibody , medicine , receptor , immune system , stimulation , immunology , lipopolysaccharide , pharmacology , endocrinology , antibody
Rheumatoid arthritis (RA) is an autoimmune disorder which shows production of autoantibodies, inflammation, bone erosion, swelling and pain in joints. In this study, we examined the effects of an immune‐modulating peptide, WKYMVm, that is an agonist for formyl peptide receptors (FPRs). Administration of WKYMVm into collagen‐induced arthritis (CIA) mice, an animal model for RA, attenuated paw thickness, clinical scores, production of type II collagen‐specific antibodies and inflammatory cytokines. WKYMVm treatment also decreased the numbers of T H 1 and T H 17 cells in the spleens of CIA mice. WKYMVm attenuated T H 1 and T H 17 differentiation in a dendritic cell (DC)‐dependent manner. WKYMVm‐induced beneficial effects against CIA and WKYMVm‐attenuated T H 1 and T H 17 differentiation were reversed by cyclosporin H but not by WRW4, indicating a crucial role of FPR1. We also found that WKYMVm augmented IL‐10 production from lipopolysaccharide‐stimulated DCs and WKYMVm failed to suppress T H 1 and T H 17 differentiation in the presence of anti‐IL‐10 antibody. The therapeutic administration of WKYMVm also elicited beneficial outcome against CIA. Collectively, we demonstrate that WKYMVm stimulation of FPR1 in DCs suppresses the generation of T H 1 and T H 17 cells via IL‐10 production, providing novel insight into the function of FPR1 in regulating CIA pathogenesis.