Tolerogenic nanoliposomes for the treatment of Rheumatoid Arthritis

Abstract

Abstract Rheumatoid arthritis (RA) is a T-cell mediated chronic inflammatory disease characterized by inflammation of the synovial joints, and cartilage and bone tissue destruction. Therapeutic approaches for the induction of immune tolerance are of high clinical significance, and approaches aimed at controlling the balance of effector and regulatory T cells in an antigen-specific manner remain an unmet medical need. Based on its role in the control of the immune response, the ligand-activated transcription factor aryl hydrocarbon receptor (AhR) represents a strong candidate target for the development of novel immunotherapies. Here, we report the development of nanoliposomes (NLPs) which co-deliver a tolerogenic AhR ligand, ITE, and collagen type IIa. These NLPs ameliorated disease symptoms in the collagen-induced arthritis (CIA) model of RA in preventive and therapeutic treatment paradigms. CIA amelioration was associated with reduced levels of pro-inflammatory cytokines in the joints and decreased collagen type II specific IgG antibodies in serum. In addition, treatment with tolerogenic NLPs induced the expansion of FoxP3+ and IL10+ regulatory T cells and suppressed collagen-specific IFNγ+ effector T cells. Taken together, these results suggest that NLPs suppressed both T-cell and B-cell pathogenic responses and represent a novel therapeutic platform to induce antigen-specific tolerance for the treatment of autoimmune diseases.