HSP70iQ435A-Encoding DNA Repigments Vitiligo Lesions in Sinclair Swine

Steven W. Henning, Manuel F. Fernandez, James P. Mahon, Richard Duff, Farshid Azarafrooz, José A. Guevara-Patiño, Alfred W. Rademaker, Andrew L. Salzman, I. Caroline Le Poole*

*Corresponding author for this work

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Human HSP70iQ435A carries a single amino-acid modification within the dendritic cell activating region and tolerizes dendritic cells in vitro. The underlying DNA was used to prevent and treat disease in vitiligo mouse models through reduced dendritic cell activation and diminished skin T-cell infiltration, suggesting the same may be useful for patients. Physiologic differences between mouse and human skin then called for studies in large animals with human-like skin. We established the efficiency of DNA jet injection into swine skin before subcloning HSP70iQ435A into clinically suitable vector pUMVC3. Vitiligo lesions in Sinclair swine were treated with plasmid DNA to measure changes in depigmentation, T-cell infiltration, expression of HSP70i in skin, serum HSP70i, and anti-HSP70i serum titers. Remarkable repigmentation following HSP70iQ435A-encoding DNA treatment persisted throughout the 6-month follow-up period. Repigmentation was accompanied by an initial influx of T cells accompanied by increased CD4/CD8 ratios, waning by week 15. Melanocytes spanned the border of repigmenting skin, suggesting that melanocyte repopulation precedes skin melanization. Serum titer fluctuations were not treatment-associated. Importantly, treatment did not interfere with melanoma immunosurveillance. These data encourage clinical testing of HSP70iQ435A.

Original languageEnglish (US)
Pages (from-to)2531-2539
Number of pages9
JournalJournal of Investigative Dermatology
Volume138
Issue number12
DOIs
StatePublished - Dec 2018

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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    Henning, S. W., Fernandez, M. F., Mahon, J. P., Duff, R., Azarafrooz, F., Guevara-Patiño, J. A., Rademaker, A. W., Salzman, A. L., & Le Poole, I. C. (2018). HSP70iQ435A-Encoding DNA Repigments Vitiligo Lesions in Sinclair Swine. Journal of Investigative Dermatology, 138(12), 2531-2539. https://doi.org/10.1016/j.jid.2018.06.186