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

Rafael R. Flores, Lana Carbo, Eun Kim, Montina Van Meter, Consuelo M.Lopez De Padilla, Jing Zhao, Debora Colangelo, Matthew J. Yousefzadeh, Luise A. Angelini, Lei Zhang, Enrico Pola, Nam Vo, Christopher H. Evans, Andrea Gambotto, Laura J. Niedernhofer, Paul D. Robbins

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Abstract

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. FASEB J. 33, 9505–9515 (2019). www.fasebj.org.

Original languageEnglish (US)
Pages (from-to)9505-9515
Number of pages11
JournalFASEB Journal
Volume33
Issue number8
DOIs
StatePublished - Aug 1 2019

Bibliographical note

Funding Information:
The authors thank Biviana Torres (The Scripps Research Institute) for her assistance with flow cytometry and Shannon Howard, Sara McGowan, and Tokio Sano (all from The Scripps Research Institute) for their assistance in collecting and the processing of tissues. The authors acknowledge and extend gratitude to Yuan Yuan Ling (retired, formerly of The Scripps Research Institute) for years of service to science. This work was supported by Grants from the U.S. National Institutes of Health (NIH) National Institute on Aging (AG024827, AG044376), NIH National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR051456), and a program grant from the Juvenile Diabetes Research Foundation to P.D.R. R.R.F. was supported by a T32 grant from NIH on Autoimmunity and Immunopathology. This project used the University of Pittsburgh Cancer Institute Vector Facilities (Pittsburgh, PA, USA) supported by the University of Pittsburgh's NIH Cancer Center Support Grant P30 CA047904. The authors declare no conflicts of interest.

Keywords

  • adenovirus
  • interleukin-17
  • interleukin-23
  • psoriasis
  • type 1 diabetes

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