LAUSR.org creates dashboard-style pages of related content for over 1.5 million academic articles. Sign Up to like articles & get recommendations!

EPCR deficiency ameliorates inflammatory arthritis in mice via suppressing the activation and migration of T cells and dendritic cells.

Photo by mertguller from unsplash

OBJECTIVES Endothelial protein C receptor (EPCR) is highly expressed in synovial tissues of patients with rheumatoid arthritis (RA), but the function of this receptor remains unknown in RA. This study… Click to show full abstract

OBJECTIVES Endothelial protein C receptor (EPCR) is highly expressed in synovial tissues of patients with rheumatoid arthritis (RA), but the function of this receptor remains unknown in RA. This study investigated the effect of EPCR on the onset and development of inflammatory arthritis and its underlying mechanisms. METHODS Collagen-induced arthritis (CIA) was induced in EPCR gene knockout (KO) and matched wild type (WT) mice. The onset and development of arthritis was monitored clinically and histologically. T cells, dendritic cells (DCs), EPCR and cytokines from EPCRKO and WT mice, RA patients and healthy controls (HC) were detected by flow cytometry and ELISA. RESULTS EPCRKO mice displayed >40% lower arthritis incidence and 50% less disease severity than WT. EPCRKO mice also had significantly less Th1/Th17 cells in synovial tissues with more DCs in circulation. Lymph nodes and synovial CD4 T cells from EPCRKO mice expressed less chemokine receptors CXCR3, CXCR5 and CCR6 than WT. In vitro, EPCRKO spleen cells contained less Th1 and more Th2 and Th17 cells than WT, and, in concordance, blocking EPCR in WT cells stimulated Th2 and Th17 cells. DCs generated from EPCRKO bone marrow were less mature and produced less matrix metalloproteinase-9. Circulating T cells from RA patients expressed higher levels of EPCR than HC cells; blocking EPCR stimulated Th2 and Treg cells in vitro. CONCLUSION Deficiency of EPCR ameliorates arthritis in CIA via inhibition of the activation and migration of pathogenic Th cells and DCs. Targeting EPCR may constitute a novel strategy for future RA treatment.

Keywords: epcrko mice; cells dendritic; arthritis; dendritic cells; mice; inflammatory arthritis

Journal Title: Rheumatology
Year Published: 2023

Link to full text (if available)


Share on Social Media:                               Sign Up to like & get
recommendations!

Related content

More Information              News              Social Media              Video              Recommended



                Click one of the above tabs to view related content.