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Immunoproteasome inhibition attenuates experimental psoriasis
Marta Del Rio Oliva1, Mark Mellett2,3, Michael Basler1,4
1Division of Immunology, Department of Biology, University of Konstanz, Konstanz, Germany.
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.
