Activation of formyl peptide receptor 1 elicits therapeutic effects against collagen‐induced arthritis

• Published in: Journal of cellular and molecular medicine Vol. 25; no. 18; pp. 8936 - 8946
• Main Authors: Park, Byunghyun, Lee, Mingyu, Kim, Sang Doo, Jeong, Yu Sun, Kim, Ji Cheol, Yang, Siyoung, Kim, Hye Young, Bae, Yoe‐Sik
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01-09-2021; John Wiley and Sons Inc
• Subjects: Animal models; Animals; Antibodies; Arthritis; Arthritis, Experimental - drug therapy; Arthritis, Rheumatoid - drug therapy; Autoantibodies; Autoimmune diseases; Bone marrow; Cartilage; Cell differentiation; Cells, Cultured; Collagen; Collagen (type II); collagen‐induced arthritis; Cytokines; dendritic cell; Dendritic cells; Disease; Flow cytometry; formyl peptide receptor; Formyl peptide receptors; Government agencies; Helper cells; Histology; Hyperplasia; Inflammation; Inflammation - drug therapy; Joint diseases; Lipopolysaccharides; Lymphocytes; Lymphocytes T; Male; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Oligopeptides - pharmacology; Original; Pathogenesis; Peptides; Receptors, Formyl Peptide - immunology; Rheumatoid arthritis; T cell; T-Lymphocytes - cytology; T-Lymphocytes - immunology; Transgenic animals; St Louis Missouri; United States > US; collagen-induced arthritis; formyl peptide receptor; rheumatoid arthritis; T cell; dendritic cell
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.16854

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 TH1 and TH17 cells in the spleens of CIA mice. WKYMVm attenuated TH1 and TH17 differentiation in a dendritic cell (DC)‐dependent manner. WKYMVm‐induced beneficial effects against CIA and WKYMVm‐attenuated TH1 and TH17 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 TH1 and TH17 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 TH1 and TH17 cells via IL‐10 production, providing novel insight into the function of FPR1 in regulating CIA pathogenesis.