HSP70i is a critical component of the immune response leading to vitiligo |
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Authors: | Mosenson Jeffrey A Zloza Andrew Klarquist Jared Barfuss Allison J Guevara-Patino Jose A Poole I Caroline Le |
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Affiliation: | Department of Pathology, Microbiology & Immunology, Oncology Institute, Loyola University, Maywood, IL, USA. |
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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. |
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Keywords: | vitiligo autoimmunity HSP70 knockout mouse |
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