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The immunoproteasome is a special form of the proteasome expressed in cells of hematopoietic origin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The therapeutic use of ONX 0914, a selective inhibitor of the immunoproteasome, was investigated in <jats:italic>Card14\u0394E138<jats:sup>+\/-<\/jats:sup><\/jats:italic> mice, which spontaneously develop psoriasis-like symptoms, and in the imiquimod murine model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats: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 \u03b1\u03b2<jats:sup>+<\/jats:sup> and \u03b3\u03b4<jats:sup>+<\/jats:sup> T cell subsets.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats: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.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2022.1075615","type":"journal-article","created":{"date-parts":[[2022,12,15]],"date-time":"2022-12-15T09:42:19Z","timestamp":1671097339000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Immunoproteasome inhibition attenuates experimental 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