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.
authors: Department of Pathology, Microbiology & Immunology, Oncology Institute, Loyola University, Maywood, IL, USA.
authors: Jeffrey A
authors: JA
authors: Mosenson
authors: Andrew
authors: A
authors: Zloza
authors: Jared
authors: J
authors: Klarquist
authors: Allison J
authors: AJ
authors: Barfuss
authors: Jose A
authors: JA
authors: Guevara-Patino
authors: I Caroline Le
authors: IC
authors: Poole
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology; D003713:Dendritic Cells / Q000473:pathology; D005260:Female; D050884:HSP72 Heat-Shock Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007249:Inflammation; D019746:Intramolecular Oxidoreductases / Q000276:immunology; D008297:Male; D008544:Melanocytes / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010088:Oxidoreductases / Q000276:immunology; D012880:Skin Pigmentation / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014611:Vaccination; D014820:Vitiligo / Q000276:immunology* / Q000473:pathology; D058951:gp100 Melanoma Antigen / Q000276:immunology
chemical_list: D001324:Autoantigens; D050884:HSP72 Heat-Shock Proteins; D058951:gp100 Melanoma Antigen; D010088:Oxidoreductases; C064056:tyrosinase-related protein-1; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase