Inducing immune tolerance through repeated administration of self-antigens is a promising strategy for treating rheumatoid arthritis (RA), and current research indicates that coadministration of immunomodulators can further orchestrate the tolerogenic response. However, most of the clinical trials based on tolerance induction have negligible therapeutic effects. Peripheral lymphoid organs play critical roles in immunotherapy. Here, we design an engineered nanoemulsion for targeted codelivery of self-antigens and an immunomodulator to ectopic lymphoid structures (ELSs) in inflamed joints of RA. Namely, a citrullinated multiepitope self-antigen (CitP) and rapamycin are incorporated into the nanoemulsions (NEs@CitP/Rapa), which are fabricated by a facial method using commercialized pharmaceutical excipients. After intravenous administration, the nanoemulsion shows satisfactory accumulation in the inflamed paws and provides enhanced anti-inflammatory effect in various experimental murine models of RA. Our study provides a promising targeting strategy to induce immune tolerance for the treatment of RA.
Keywords: Citrullinated multiepitope self-antigen; Ectopic lymphoid structures; Immune tolerance; Nanoemulsions; Rapamycin; Rheumatoid arthritis.