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HSP70i is a critical component of the immune response leading to vitiligo
Author(s) -
Mosenson Jeffrey A.,
Zloza Andrew,
Klarquist Jared,
Barfuss Allison J.,
GuevaraPatino Jose A.,
Le Poole I. Caroline
Publication year - 2012
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/j.1755-148x.2011.00916.x
Subject(s) - depigmentation , vitiligo , immune system , biology , knockout mouse , cytotoxic t cell , hsp70 , immunology , hair follicle , t cell , heat shock protein , cancer research , microbiology and biotechnology , in vitro , genetics , gene
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.