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The immunoproteasome: a novel drug target for autoimmune diseases

1, 2, 3, 4, 5

  1. Division of Immunology, Department of Biology, University of Konstanz, Germany; and Biotechnology Institute Thurgau (BITg) at the University of Konstanz, Kreuzlingen, Switzerland. michael.basler@uni-konstanz.de
  2. Division of Immunology, Department of Biology, University of Konstanz, Konstanz, Germany.
  3. Division of Immunology, Department of Biology, University of Konstanz, Konstanz, Germany.
  4. Division of Immunology, Department of Biology, University of Konstanz, Konstanz, Germany.
  5. Division of Immunology, Department of Biology, University of Konstanz, Germany; and Biotechnology Institute Thurgau (BITg) at the University of Konstanz, Kreuzlingen, Switzerland. marcus.groettrup@uni-konstanz.de

Division of Immunology, Department of Biology, University of Konstanz, Germany.

CER8911 Submission on line
2015 Vol.33, N°4 ,Suppl.92 - PI 0074, PF 0079
Special Lecture

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Rheumatology Article

 

Abstract

The immunoproteasome, a special class of the proteasome, is mainly expressed in cells of haematopoietic origin. Additionally, during inflammation, the immunoproteasome is induced by IFN-γ or TNF-α. In recent years it became apparent that the immunoproteasome has important functions other than processing proteins for MHC class I restricted presentation. The immunoproteasome plays a critical role in T cell expansion, cytokine production, and T helper cell differentiation. Inhibition of the immunoproteasome ameliorated disease symptoms in different animal models for autoimmune diseases. Hence, the unique role for LMP7 in controlling pathogenic immune responses provides a therapeutic rationale for targeting LMP7 in autoimmune disorders. In this review we summarise the effect of immunoproteasome inhibition in animal models for rheumatoid arthritis, inflammatory bowel disease, Hashimoto’s thyroiditis, systemic lupus erythematosus, and multiple sclerosis.

PMID: 26458097 [PubMed]

Received: 28/08/2015 - Accepted : 01/09/2015 - In Press: 12/10/2015 - Published: 14/10/2015