HSP70i is a critical component of the immune response leading to vitiligo. Journal Article


Authors: Mosenson, J. A.; Zloza, A.; Klarquist, J.; Barfuss, A. J.; Guevara-Patino, J. A.; Poole, I. C.
Article Title: HSP70i is a critical component of the immune response leading to vitiligo.
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. Copyright 2011 John Wiley Sons A/S.
Keywords: Female; Male; Animals; Mice; Mice, Inbred C57BL; Mice, Transgenic; Oncology Institute; Inflammation; Mice, Knockout; Vaccination; vitiligo; Autoantigens; Autoimmune Diseases; Dendritic Cells; HSP72 Heat-Shock Proteins; Intramolecular Oxidoreductases; Melanocytes; Oxidoreductases; Skin Pigmentation; T-Lymphocytes, Cytotoxic; gp100 Melanoma Antigen
Journal Title: Pigment cell melanoma research
Volume: 25
Issue: 1
ISSN: 1755-148X; 1755-1471
Publisher: Wiley Periodicals, Inc  
Journal Place: England
Date Published: 2012
Start Page: 88
End Page: 98
Language: English
DOI/URL:
Notes: ID: 12122; Record Owner: From MEDLINE, a database of the U.S. National Library of Medicine.; Status: MEDLINE; Publishing Model: Journal available in: Print-Electronic Citation processed from: Internet; NLM Journal Code: 101318927; CAS Registry/EC Number/Name of Substance: 0 (Autoantigens). 0 (HSP72 Heat-Shock Proteins). 0 (gp100 Melanoma Antigen). EC 1 (Oxidoreductases). EC 1-14-18 (tyrosinase-related protein-1). EC 5-3 (Intramolecular Oxidoreductases). EC 5-3-3-12 (dopachrome isomerase).; Grant Number: R01 AR054749 (United States NIAMS NIH HHS); Electronic Date of Publication: 20111114; Entry Date: 20120306