4.8 Article

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

Journal

FRONTIERS IN IMMUNOLOGY
Volume 12, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.614320

Keywords

psoriasis; regulatory T cells; Treg; Th17; heat shock proteins; Hsp70; immunization

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Funding

  1. Polish National Science Centre (NCN) [2017/25/B/NZ6/00305]
  2. Cluster of Excellence Precision Medicine in Chronic Inflammation from the Deutsche Forschungsgemeinschaft [EXC 2167]

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The study found that Hsp70 immunization and anti-Hsp70 antibody treatment can decrease disease severity in a psoriasis-like skin inflammation mouse model by affecting T cell populations. This suggests that Hsp70 may be a promising therapeutic target for psoriasis and other autoimmune dermatoses.
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.

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