AUTHOR=del Rio Oliva Marta , Mellett Mark , Basler Michael 

TITLE=Immunoproteasome inhibition attenuates experimental psoriasis

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1075615

DOI=10.3389/fimmu.2022.1075615

ISSN=1664-3224

ABSTRACT=<sec><title>Introduction</title><p>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.</p></sec><sec><title>Methods</title><p>The therapeutic use of ONX 0914, a selective inhibitor of the immunoproteasome, was investigated in <italic>Card14ΔE138<sup>+/-</sup></italic> mice, which spontaneously develop psoriasis-like symptoms, and in the imiquimod murine model.</p></sec><sec><title>Results</title><p>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<sup>+</sup> and γδ<sup>+</sup> T cell subsets.</p></sec><sec><title>Discussion</title><p>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.</p></sec>