HSP70i accelerates depigmentation in a mouse model of autoimmune vitiligo.
Vitiligo is a T-cell-mediated autoimmune disease of the skin. Progressive depigmentation accelerates in response to stress. Personal trauma, contact with bleaching phenols, overexposure to UV, and mechanical injury can lead to progressive loss of melanocytes. This study was focused on the role of stress protein heat shock protein (HSP)70 for translating stress into an autoimmune disease to melanocytes. Intracellular HSP70 can act as a cytoprotectant, preventing apoptosis in cells under stress. Isoform HSP70i can be secreted by live cells, and in prior in vitro studies, HSP70 has been shown to activate dendritic cells and elicit an immune response to chaperoned proteins and peptides. Here, the role of HSP70 in precipitating and perpetuating vitiligo was assessed in vivo in a mouse model of autoimmune vitiligo. In this model, depigmentation was introduced by gene gun vaccination with eukaryotic expression plasmids encoding melanocyte differentiation antigens. Inclusion of human and mouse-derived inducible HSP70 in the vaccination protocol significantly increased and accelerated depigmentation in this model, accompanied by the induction of prolonged humoral responses to HSP70. Cytotoxicity toward targets loaded with a K(b)-restricted tyrosinase-related protein 2-derived peptide correlated with depigmentation. The data presented strongly support a role for HSP70i in progressive depigmentation in vivo.
Denman
Cecele J
CJ
Department of Pathology/Oncology Institute, Loyola University Chicago, Chicago, Illinois 60153, USA.
McCracken
James
J
Hariharan
Vidhya
V
Klarquist
Jared
J
Oyarbide-Valencia
Kepa
K
Guevara-Patiño
José A
JA
Le Poole
I Caroline
IC
D000818:Animals; D001327:Autoimmune Diseases / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D008544:Melanocytes / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D020033:Protein Isoforms / Q000378:metabolism; D012880:Skin Pigmentation; D014820:Vitiligo / Q000378:metabolism* / Q000473:pathology
D018840:HSP70 Heat-Shock Proteins; D015395:Histocompatibility Antigens Class I; D020033:Protein Isoforms; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase