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Proteasome function shapes innate and adaptive immune responses.

Am. J. Physiol. Lung Cell Mol. Physiol. 311, L328-L336 (2016)
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The proteasome system degrades more than 80% of intracellular proteins into small peptides. Accordingly, the proteasome is involved in many essential cellular functions such as protein quality control, transcription, immune responses, cell signaling, and apoptosis. Moreover, degradation products are loaded onto major histocompatibility (MHC) class I molecules to communicate the intracellular protein composition to the immune system. The standard 20S proteasome core complex contains three distinct catalytic active sites that are exchanged upon stimulation with inflammatory cytokines to form the so-called immunoproteasome. Immunoproteasomes are constitutively expressed in immune cells and have different proteolytic activities compared to standard proteasomes. They are rapidly induced in parenchymal cells upon intracellular pathogen infection and are crucial for priming effective CD8+ T cell-mediated immune responses against infected cells. Beyond shaping these adaptive immune reactions, immunoproteasomes also regulate the function of immune cells by degradation of inflammatory and immune mediators. Accordingly, they emerge as novel regulators of innate immune responses. The recently unraveled impairment of immunoproteasome function by environmental challenges and by genetic variations of immunoproteasome genes might represent a currently underestimated risk factor for the development and progression of lung diseases. In particular, immunoproteasome dysfunction will dampen resolution of infections thereby promoting exacerbations, may foster autoimmunity in chronic lung diseases, and possibly contributes to immune evasion of tumor cells. Novel pharmacological tools such as site-specific inhibitors of the immunoproteasome as well as activity-based probes, however, hold promises as novel therapeutic drugs for respiratory diseases and biomarker profiling, respectively.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Adaptive Immunity ; Immunoproteasome ; Immunoproteasome Inhibitor ; Innate Immune Response ; Lung Disease; Immunoproteasome Subunit Lmp7; T-cell Responses; Obstructive Pulmonary-disease; Induced Oxidative Stress; Antigen Presentation; Selective Inhibitor; Constitutive Proteasome; Epitope Generation; Damaged Proteins; Cigarette-smoke
ISSN (print) / ISBN 1040-0605
e-ISSN 1522-1504
Quellenangaben Band: 311, Heft: 2, Seiten: L328-L336 Artikelnummer: , Supplement: ,
Verlag American Physiological Society
Verlagsort Bethesda, Md. [u.a.]
Begutachtungsstatus Peer reviewed