Adenoviral gene transfer of a single-chain IL-23 induces psoriatic arthritis-like symptoms in NOD mice.

Previously, we demonstrated that intratumoral delivery of adenoviral vector encoding single-chain (sc)IL-23 (Ad.scIL-23) was able to induce systemic antitumor immunity. Here, we examined the role of IL-23 in diabetes in nonobese diabetic 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 T helper type 17 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 arthritis for understanding disease progression and for testing therapeutic approaches.-Flores, R. R., Carbo, L., Kim, E., Van Meter, M., De Padilla, C. M. L., Zhao, J., Colangelo, D., Yousefzadeh, M. J., Angelini, L. A., Zhang, L., Pola, E., Vo, N., Evans, C. H., Gambotto, A., Niedernhofer, L. J., Robbins, P. D. Adenoviral gene transfer of a single-chain IL-23 induces psoriatic arthritis-like symptoms in NOD mice.

Dendritic cells and the immunopathogenesis of idiopathic inflammatory myopathies.

PURPOSE OF REVIEW: Mechanisms driving the autoimmune process in idiopathic inflammatory myopathies (IIMs) have not been unraveled, despite extensive studies. In recent times, it has become apparent that heterogeneous populations of dendritic cells have specialized roles in IIM. Here, we will discuss the role of dendritic cells in the induction of adaptive immune response in IIM and review the recent literature addressing the role of dendritic cells in the cause and pathogenesis of inflammatory myopathies. RECENT FINDINGS: Different subsets of immature and mature dendritic cells have been recently identified in skeletal muscle in IIM. Dendritic cells present in inclusion body myositis and polymyositis are primarily myeloid dendritic cells. In contrast, plasmacytoid dendritic cells, a subset of dendritic cells and considered the main source of the interferon-alpha/beta (IFN-alpha/beta), have been found abundantly in muscle tissue of adult dermatomyositis and juvenile dermatomyositis. SUMMARY: Dendritic cells are associated with the chronic infiltration of mononuclear cells in the inflammatory muscle tissue of IIM patients. Increasing evidences point out that dendritic cells are not only crucially involved in the initiation of anti-self immune response but are also essential for the maintenance of autoimmune lesions in inflammatory myopathies.