Immunosuppressive Cytokine‐Tethered Hydrogel for Treating Rheumatoid Arthritis

An injectable hydrogel is developed by chemically tethering IL-4, an immunosuppressive cytokine, to a hyaluronic acid-based backbone. The hydrogel reduces joint friction and exerts immunomodulatory effects. In a rheumatoid arthritis (RA) mouse model, it reduced inflammation, preserved cartilage, and promoted anti-inflammatory immune responses. This platform may be extended to treat other autoimmune and inflammatory diseases beyond RA.

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by persistent inflammation and progressive joint destruction. Current therapies primarily rely on general immune suppression, often leading to suboptimal outcomes and significant side effects. To address these challenges, an interleukin-4 (IL-4)-tethered, hyaluronic acid-based hydrogel is developed that withstands repeated mechanical stress in the joint space while fostering an immunomodulatory environment. The immunosuppressive hydrogel promotes anti-inflammatory M2 macrophage polarization, creating an anti-inflammatory microenvironment while preserving cartilage and mitigating joint damage. The mechanical properties of the hydrogel are carefully optimized for injectability and intra-articular application. Its effectiveness is evaluated in a collagen-induced arthritis (CIA) mouse model, demonstrating potential as a localized therapeutic approach. It is believed that this IL-4-tethered hydrogel platform will provide a foundation for the combinatorial treatment of RA and various inflammatory diseases.