Immunoproteasome inhibition attenuates experimental psoriasis

Front Immunol. 2022 Dec 14:13:1075615. doi: 10.3389/fimmu.2022.1075615. eCollection 2022.

Abstract

Introduction: Psoriasis is an autoimmune skin disease associated with multiple comorbidities. The immunoproteasome is a special form of the proteasome expressed in cells of hematopoietic origin.

Methods: The therapeutic use of ONX 0914, a selective inhibitor of the immunoproteasome, was investigated in Card14ΔE138+/- mice, which spontaneously develop psoriasis-like symptoms, and in the imiquimod murine model.

Results: In both models, treatment with ONX 0914 significantly reduced skin thickness, inflammation scores, and pathological lesions in the analyzed skin tissue. Furthermore, immunoproteasome inhibition normalized the expression of several pro-inflammatory genes in the ear and significantly reduced the inflammatory infiltrate, accompanied by a significant alteration in the αβ+ and γδ+ T cell subsets.

Discussion: ONX 0914 ameliorated psoriasis-like symptoms in two different murine psoriasis models, which supports the use of immunoproteasome inhibitors as a therapeutic treatment in psoriasis.

Keywords: CARD14; ONX 0914; imiquimod; immunoproteasome inhibition; psoriasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoimmune Diseases*
  • Inflammation / pathology
  • Mice
  • Proteasome Inhibitors / pharmacology
  • Proteasome Inhibitors / therapeutic use
  • Psoriasis* / drug therapy
  • Skin / pathology

Substances

  • Proteasome Inhibitors

Grants and funding

This work was supported by the “Forschungspreis Walter Enggist”, Kezar Life Science, and the German Research Foundation (DFG) grant GR 1517/27-1 and SFB969 project C01. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.