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

Stefan Tukaj*, Jagoda Mantej, Michał Sobala, Katarzyna Potrykus, Zbigniew Tukaj, Detlef Zillikens, Ralf J. Ludwig, Katja Bieber, Michael Kasperkiewicz

*Corresponding author for this work
1 Citation (Scopus)

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.

Original languageEnglish
Article number614320
JournalFrontiers in Immunology
Volume12
Pages (from-to)614320
ISSN1664-3224
DOIs
Publication statusPublished - 23.02.2021

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)
  • Centers: Center for Research on Inflammation of the Skin (CRIS)

DFG Research Classification Scheme

  • 2.21-05 Immunology
  • 2.22-19 Dermatology

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  • CRC 1526, PANTAU: Pathomechanisms of Antibody-mediated Autoimmunity

    Sadik, C. (Speaker, Coordinator), Zillikens, D. (Speaker, Coordinator), Scheffold, A. (Principal Investigator (PI)), Schmidt, E. (Principal Investigator (PI)), Heine, G. (Principal Investigator (PI)), Manz, R. (Principal Investigator (PI)), Köhl, J. (Principal Investigator (PI)), Ludwig, R. (Principal Investigator (PI)), Peipp, M. (Principal Investigator (PI)), Hammers, M. C. (Principal Investigator (PI)), Verschoor, A. (Principal Investigator (PI)), Karsten, C. (Principal Investigator (PI)), Nimmerjahn, F. (Principal Investigator (PI)), Hutloff, A. (Principal Investigator (PI)), Ibrahim, S. (Principal Investigator (PI)), Wettschureck, N. (Principal Investigator (PI)), Bieber, K. (Principal Investigator (PI)), Schilf, P. (Principal Investigator (PI)), Vaeth, M. (Principal Investigator (PI)), Hirose, M. (Principal Investigator (PI)), Vaeth, M. (Principal Investigator (PI)), Baines, J. F. (Principal Investigator (PI)), Bacher, P. (Principal Investigator (PI)), Hoffmann, M. (Principal Investigator (PI)), Busch, H. S. (Principal Investigator (PI)), Höppner, M. (Principal Investigator (PI)), Becker, M. (Principal Investigator (PI)), Holtsche, M. M. (Principal Investigator (PI)), Fähnrich, A. (Principal Investigator (PI)), Szymczak, S. (Principal Investigator (PI)), Murthy, S. (Principal Investigator (PI)) & Lux, A. (Principal Investigator (PI))

    01.01.22 → …

    Project: DFG ProjectsDFG Joint Research: Collaborative Research Center/ Transregios

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