Evidence for a role of extracellular heat shock protein 70 in epidermolysis bullosa acquisita.

Abstract

Heat shock protein 90 (Hsp90) and Hsp70 are chaperones implicated in different inflammatory disorders, given their property to impact innate and adaptive immune responses. Here, we determined the so far unknown role of extracellular Hsp70 in epidermolysis bullosa acquisita (EBA), an anti-type VII collagen autoantibody-mediated blistering dermatosis. The in vivo pathophysiological relevance of extracellular Hsp70 was demonstrated in an anti-type VII collagen antibody transfer-induced EBA mouse model in which elevated blood levels of this chaperone were recorded. We found that Hsp70-treated mice had a more intense clinical disease severity compared to controls that were paralleled by increased levels of cutaneous matrix metalloproteinase 9 and plasma hydrogen peroxide. The latter finding was confirmed in an independent reactive oxygen species release assay using EBA-specific immune complexes combined with recombinant Hsp70. Finally, cell culture experiments using human naive peripheral blood mononuclear cells (PBMC) revealed that extracellular Hsp70 stimulated the secretion of the T cell-derived pro-inflammatory cytokines IL-6 and IL-8. This work extends knowledge about the role of Hsps in autoimmune bullous diseases, suggesting that extracellular Hsp70 represents a pathophysiological factor and potential treatment target in EBA.

• Authors: Stefan Tukaj, Jagoda Mantej, Krzysztof Sitko, Marta Bednarek, Detlef Zillikens, Ralf J Ludwig, Katja Bieber, Michael Kasperkiewicz
• Journal: Experimental dermatology (Exp Dermatol) Vol. 31 Issue 4 Pg. 528-534 (04 2022) ISSN: 1600-0625 [Electronic] Denmark
• PMID: 34741567 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemical References

• Autoantibodies
• Collagen Type VII
• HSP70 Heat-Shock Proteins
• anti-type VII collagen autoantibody

Topics

• Animals
• Autoantibodies
• Autoimmune Diseases
• Collagen Type VII
• Epidermolysis Bullosa Acquisita
• HSP70 Heat-Shock Proteins
• Leukocytes, Mononuclear (metabolism)
• Mice