Nature-inspired IL-1 targeted therapy to treat chronic inflammatory diseases.

ABSTRACT: The interleukin (IL)-1 pathway is a key mediator of inflammation and innate immune responses. Its dysregulation contributes to rheumatoid arthritis (RA) and autoinflammatory diseases (AIDs). In this study, we develop a recombinant adeno-associated virus (rAAV)-based gene therapy to deliver an inflammation-inducible, secreted human IL-1 receptor antagonist (sIL-1Ra) as a complementary approach to existing IL-1 blockers. rAAV-mediated expression of sIL-1Ra dampens IL-1 signaling and inflammatory arthritis in mice. As the expression of endogenous sIL-1Ra is tightly regulated by inflammation, we developed an rAAV vector that produces sIL-1Ra in response to pro-inflammatory cytokines and bone morphogenic proteins (BMPs) enriched in the inflamed joints of patients with RA. Remarkably, inflammati

SUBMITTER: Yang YS 

PROVIDER: S-EPMC12466080 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature