title: The immunoproteasome: a novel drug target for autoimmune diseases.
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.
authors.affiliation: 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.
authors.forename: Michael
authors.initials: M
authors.lastname: Basler
authors.affiliation: Division of Immunology, Department of Biology, University of Konstanz, Konstanz, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Mundt
authors.affiliation: Division of Immunology, Department of Biology, University of Konstanz, Konstanz, Germany.
authors.forename: Annegret
authors.initials: A
authors.lastname: Bitzer
authors.affiliation: Division of Immunology, Department of Biology, University of Konstanz, Konstanz, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Schmidt
authors.affiliation: 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.
authors.forename: Marcus
authors.initials: M
authors.lastname: Groettrup
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D055808:Drug Discovery; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D058990:Molecular Targeted Therapy; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D061988:Proteasome Inhibitors / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D007155:Immunologic Factors; D061988:Proteasome Inhibitors; C077436:LMP7 protein; D046988:Proteasome Endopeptidase Complex