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HSP70I IS A CRITICAL COMPONENT OF THE IMMUNE RESPONSE LEADING TO VITILIGO
- Publication Year :
- 2011
-
Abstract
- HSP70i and other stress proteins have been used in anti-tumor vaccines. This begs the question whether HSP70i plays a unique role in immune activation. We vaccinated inducible HSP70i (Hsp70-1) knockout mice and wild-type animals with optimized TRP-1, a highly immunogenic melanosomal target molecule. We were unable to induce robust and lasting depigmentation in the Hsp70-1 knockout mice, and in vivo cytolytic assays revealed a lack of cytotoxic T-lymphocyte activity. Absence of T-cell infiltration to the skin and maintenance of hair follicle melanocytes were observed. By contrast, depigmentation proceeded without interruption in mice lacking a tissue-specific constitutive isoform of HSP70 (Hsp70-2) vaccinated with TRP-2. Next, we demonstrated that HSP70i was necessary and sufficient to accelerate depigmentation in vitiligo-prone Pmel-1 mice, accompanied by lasting phenotypic changes in dendritic cell subpopulations. In summary, these studies assign a unique function to HSP70i in vitiligo and identify HSP70i as a targetable entity for treatment.
- Subjects :
- Inflammation
Male
Mice, Knockout
Vaccination
Vitiligo
HSP72 Heat-Shock Proteins
Mice, Transgenic
Skin Pigmentation
Dendritic Cells
Autoantigens
Article
Autoimmune Diseases
Intramolecular Oxidoreductases
Mice, Inbred C57BL
Mice
Animals
Melanocytes
Female
Oxidoreductases
T-Lymphocytes, Cytotoxic
gp100 Melanoma Antigen
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.pmid..........5e8bcb369bc904c87cc5ef9df7464f8c