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ORIGINAL ARTICLE
HSP70i is a critical component of the immune response leading to vitiligo
Article first published online: 14 NOV 2011
DOI: 10.1111/j.1755-148X.2011.00916.x
© 2011 John Wiley & Sons A/S
Additional Information
How to Cite
Mosenson, J. A., Zloza, A., Klarquist, J., Barfuss, A. J., Guevara-Patino, J. A. and Le Poole, I. C. (2012), HSP70i is a critical component of the immune response leading to vitiligo. Pigment Cell & Melanoma Research, 25: 88–98. doi: 10.1111/j.1755-148X.2011.00916.x
Publication History
- Issue published online: 16 DEC 2011
- Article first published online: 14 NOV 2011
- Accepted manuscript online: 6 OCT 2011 07:39AM EST
- PUBLICATION DATA Received 26 April 2011, revised and accepted for publication 30 September 2011,published online 6 October 2011
Keywords:
- vitiligo;
- autoimmunity;
- HSP70;
- knockout mouse
Summary
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.