HSP70iQ435A-Encoding DNA Repigments Vitiligo Lesions in Sinclair Swine
| Autor: | José A. Guevara-Patiño, I. Caroline Le Poole, Manuel F. Fernandez, Richard Duff, Andrew L. Salzman, Steven W. Henning, James P. Mahon, Alfred Rademaker, Farshid Azarafrooz |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty integumentary system business.industry Melanoma Human skin Cell Biology Dermatology Vitiligo Dendritic cell Melanocyte medicine.disease Biochemistry Immunosurveillance 03 medical and health sciences 030104 developmental biology medicine.anatomical_structure Depigmentation medicine medicine.symptom business Molecular Biology CD8 |
| Zdroj: | Journal of Investigative Dermatology. 138:2531-2539 |
| ISSN: | 0022-202X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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