Therapeutic Implications of Targeting Heat Shock Protein 70 by Immunization or Antibodies in Experimental Skin Inflammation.

Abstract	Heat shock proteins (Hsp) are constitutive and stress-induced molecules which have been reported to impact innate and adaptive immune responses. Here, we evaluated the role of Hsp70 as a treatment target in the imiquimod-induced, psoriasis-like skin inflammation mouse model and related in vitro assays. We found that immunization of mice with Hsp70 resulted in decreased clinical and histological disease severity associated with expansion of T cells in favor of regulatory subtypes (CD4+FoxP3+/CD4+CD25+ cells). Similarly, anti-Hsp70 antibody treatment led to lowered disease activity associated with down-regulation of pro-inflammatory Th17 cells. A direct stimulating action of Hsp70 on regulatory T cells and its anti-proliferative effects on keratinocytes were confirmed in cell culture experiments. Our observations suggest that Hsp70 may be a promising therapeutic target in psoriasis and potentially other autoimmune dermatoses.
Authors	Stefan Tukaj, Jagoda Mantej, Michał Sobala, Katarzyna Potrykus, Zbigniew Tukaj, Detlef Zillikens, Ralf J Ludwig, Katja Bieber, Michael Kasperkiewicz
Journal	Frontiers in immunology (Front Immunol) Vol. 12 Pg. 614320 ( 2021) ISSN: 1664-3224 [Electronic] Switzerland
PMID	33708208 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright	Copyright © 2021 Tukaj, Mantej, Sobala, Potrykus, Tukaj, Zillikens, Ludwig, Bieber and Kasperkiewicz.
Chemical References	Antibodies Biomarkers Cytokines HSP70 Heat-Shock Proteins Inflammation Mediators Recombinant Proteins
Topics	Animals Antibodies (immunology, pharmacology) Biomarkers Biopsy Cytokines (metabolism) Dermatitis (diagnosis, drug therapy, etiology, metabolism) Disease Models, Animal Disease Susceptibility (immunology) Female HSP70 Heat-Shock Proteins (antagonists & inhibitors, genetics, immunology) Immunization Immunophenotyping Inflammation Mediators (metabolism) Keratinocytes (drug effects, metabolism) Mice Recombinant Proteins T-Lymphocytes, Regulatory (drug effects, immunology, metabolism) Th17 Cells (drug effects, immunology, metabolism)

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