A New Strategy in Modulating the Protease-Activated Receptor 2 (Par2) in Autoimmune Diseases

Autoimmune diseases are complex conditions characterized by immune-mediated tissue damage and chronic inflammation. Protease-activated receptor 2 (Par2) has been implicated in these diseases, exhibiting dual roles that complicate its therapeutic potential. This review examines the perplexing functions of Par2, which promotes inflammation through immune cell activation while facilitating tissue healing in damaged organs. By analyzing findings across diverse autoimmune conditions, including rheumatoid arthritis, type 1 diabetes, and inflammatory bowel disease, we highlight how the context and location of Par2 activation determine its effects. Recent studies from our laboratory have resolved some of these contradictions by distinguishing Par2’s immune-mediated inflammatory roles from its tissue-reparative functions. These insights pave the way for context-specific therapeutic strategies, such as selective Par2 modulators, that can mitigate inflammation while enhancing tissue repair. However, achieving such precision in modulation remains a significant challenge, necessitating further research into Par2’s signaling pathways. This review underscores Par2’s complexity and its transformative potential in autoimmune disease management, offering a nuanced perspective on its duality and therapeutic implications.