Adenoviral Gene Transfer of a Single Chain IL-23 Induces Psoriatic Arthritis-Like Symptoms in NOD Mice

Abstract

Summary: Previously we demonstrated that intra-tumoral delivery of adenoviral vector encoding single chain IL-23 (Ad.scIL-23) was able to induce systemic antitumor immunity. Here we examined the role of IL-23 in diabetes in NOD mice. Intravenous delivery of Ad.scIL-23 did not accelerate the onset of hyperglycemia, but instead resulted in the development of psoriatic arthritis. Ad.scIL-23 treated mice developed erythema, scales and thickening of the skin as well as intervertebral disc degeneration and extensive synovial hypertrophy and loss of articular cartilage in the knees. Immunological analysis revealed activation of conventional Th17 cells and IL-17 producing γδ T cells along with a significant depletion and suppression of T cells in the pancreatic lymph nodes. Furthermore, treatment with anti-IL-17 antibody reduced joint and skin psoriatic arthritis pathologies. Thus, these Ad.scIL-23 treated mice represent a physiologically relevant model of psoriatic arthritic for understanding disease progression and for testing therapeutic approaches. Funding Statement: This work was supported by grants AG024827, AR051456, and AG044376 from the National Institutes of Health and a program grant from the Juvenile Diabetes Research Foundation (JDRF) to PDR. RRF was supported by a T32 grant from NIH on Autoimmunity and Immunopathology. This project used the University of Pittsburgh Cancer Institute (UPCI) Vector Facilities supported by the University of Pittsburgh’s National Institutes of Health (NIH) Cancer Center Support Grant (CCSG) P30 CA047904. Declaration of Interests: The authors declare no competing financial interests. Ethics Approval Statement: All procedures performed were approved by The Scripps Research Institute-Florida Institutional Animal Care and Use Committee.