Regulation of immunoproteasome function in the lung

Ilona E. Keller, Oliver Vosyka, Shinji Takenaka, Alexander Kloß, Burkhardt Dahlmann, Lianne I. Willems, Martijn Verdoes, Hermen S. Overkleeft, Elisabeth Marcos, Serge Adnot, Stefanie M. Hauck, Clemens Ruppert, Andreas Günther, Susanne Herold, Shinji Ohno, Heiko Adler, Oliver Eickelberg, Silke Meiners*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Impaired immune function contributes to the development of chronic obstructive pulmonary disease (COPD). Disease progression is further exacerbated by pathogen infections due to impaired immune responses. Elimination of infected cells is achieved by cytotoxic CD8+ T cells that are activated by MHC I-mediated presentation of pathogen-derived antigenic peptides. The immunoproteasome, a specialized form of the proteasome, improves generation of antigenic peptides for MHC I presentation thereby facilitating anti-viral immune responses. However, immunoproteasome function in the lung has not been investigated in detail yet. In this study, we comprehensively characterized the function of immunoproteasomes in the human and murine lung. Parenchymal cells of the lung express low constitutive levels of immunoproteasomes, while they are highly and specifically expressed in alveolar macrophages. Immunoproteasome expression is not altered in whole lung tissue of COPD patients. Novel activity-based probes and native gel analysis revealed that immunoproteasome activities are specifically and rapidly induced by IFNγ treatment in respiratory cells in vitro and by virus infection of the lung in mice. Our results suggest that the lung is potentially capable of mounting an immunoproteasome-mediated efficient adaptive immune response to intracellular infections.

Original languageEnglish
Article number10230
Number of pages12
JournalScientific Reports
Publication statusPublished - 19 May 2015

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