Basler Michael, Mundt Sarah, Bitzer Annegret, Schmidt Christian, Groettrup Marcus
Division of Immunology, Department of Biology, University of Konstanz, Germany; and Biotechnology Institute Thurgau (BITg) at the University of Konstanz, Kreuzlingen, Switzerland.
Division of Immunology, Department of Biology, University of Konstanz, Konstanz, Germany.
Clin Exp Rheumatol. 2015 Jul-Aug;33(4 Suppl 92):S74-9. Epub 2015 Oct 12.
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.
免疫蛋白酶体是蛋白酶体的一种特殊类型，主要在造血起源的细胞中表达。此外，在炎症过程中，免疫蛋白酶体由干扰素-γ或肿瘤坏死因子-α诱导产生。近年来，人们逐渐认识到免疫蛋白酶体除了在处理蛋白质以供MHC I类限制性呈递方面具有重要功能外，还发挥着其他重要作用。免疫蛋白酶体在T细胞扩增、细胞因子产生和辅助性T细胞分化中起着关键作用。在不同的自身免疫性疾病动物模型中，抑制免疫蛋白酶体可改善疾病症状。因此，LMP7在控制致病性免疫反应中的独特作用为自身免疫性疾病中靶向LMP7提供了治疗依据。在本综述中，我们总结了免疫蛋白酶体抑制在类风湿性关节炎、炎症性肠病、桥本甲状腺炎、系统性红斑狼疮和多发性硬化症动物模型中的作用。
