Immunoproteasome

Abstract

The immunoproteasome is a proteolytic complex whose five subunits, β1i, β2i, β5i, PA28α and PA28β, are replaced with subunits in the constitutive proteasome. It plays an important role in the immune system and the pathogenesis of inflammatory diseases. In addition, the immunoproteasome regulates the polarisation of immune cells such as M2 macrophages and Th1 and Th17 lymphocytes. While expression of the immunoproteasome is dominant in haematopoietic cells, nonhaematopoietic cells in various peripheral tissues also express the immunoproteasome, and its expression is enhanced by inflammatory cytokines and stress signals. Recent studies indicate that each subunit of the immunoproteasome plays a unique role in nonhaematopoietic cells. For instance, β5i plays a critical role in adipogenesis and metabolic disorders. Furthermore, genetical mutation of the immunoproteasome subunits causes autoinflammatory diseases and lipodystrophy. Key Concepts The immunoproteasome plays an important role in the immune system. The immunoproteasome is involved in the pathogenesis of inflammatory diseases. Inhibition of the immunoproteasome is useful as a treatment for inflammatory diseases and tumours. The immunoproteasome plays a unique role in nonhaematopoietic cells. Deficiency of the immunoproteasome influences endocrine metabolic functions. Mutation of the immunoproteasome subunit is associated with autoinflammatory diseases and lipodystrophy.