Platelets Amplify Inflammation in Arthritis via Collagen-Dependent Microparticle Production

TLDR

Platelets participate in inflammatory responses beyond their known roles in thrombosis and wound repair. The study examined platelet involvement in rheumatoid arthritis. The authors demonstrated that collagen receptor GPVI triggers platelet microparticle production in arthritis using pharmacologic and genetic approaches. Platelet microparticles are found in joint fluid of inflammatory arthritis, elicit IL‑1–mediated cytokine responses from synovial fibroblasts, and their depletion reduces arthritis severity, revealing a novel platelet‑driven inflammatory pathway.

Abstract

In addition to their pivotal role in thrombosis and wound repair, platelets participate in inflammatory responses. We investigated the role of platelets in the autoimmune disease rheumatoid arthritis. We identified platelet microparticles--submicrometer vesicles elaborated by activated platelets--in joint fluid from patients with rheumatoid arthritis and other forms of inflammatory arthritis, but not in joint fluid from patients with osteoarthritis. Platelet microparticles were proinflammatory, eliciting cytokine responses from synovial fibroblasts via interleukin-1. Consistent with these findings, depletion of platelets attenuated murine inflammatory arthritis. Using both pharmacologic and genetic approaches, we identified the collagen receptor glycoprotein VI as a key trigger for platelet microparticle generation in arthritis pathophysiology. Thus, these findings demonstrate a previously unappreciated role for platelets and their activation-induced microparticles in inflammatory joint diseases.