title: Regulation of immunoproteasome function in the lung.
abstract: 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.
authors.affiliation: Comprehensive Pneumology Center (CPC), University Hospital, Ludwig-Maximilians University, Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), Munich, Germany.
authors.forename: Ilona E
authors.initials: IE
authors.lastname: Keller
authors.affiliation: 1] Comprehensive Pneumology Center (CPC), University Hospital, Ludwig-Maximilians University, Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), Munich, Germany [2] Research Unit Protein Science, Helmholtz Zentrum München, Munich, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Vosyka
authors.affiliation: Comprehensive Pneumology Center (CPC), University Hospital, Ludwig-Maximilians University, Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), Munich, Germany.
authors.forename: Shinji
authors.initials: S
authors.lastname: Takenaka
authors.affiliation: Institute of Biochemistry, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kloß
authors.affiliation: Institute of Biochemistry, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Burkhardt
authors.initials: B
authors.lastname: Dahlmann
authors.affiliation: Department of Bio-organic Synthesis, Leiden University, Leiden, The Netherlands.
authors.forename: Lianne I
authors.initials: LI
authors.lastname: Willems
authors.affiliation: Department of Bio-organic Synthesis, Leiden University, Leiden, The Netherlands.
authors.forename: Martijn
authors.initials: M
authors.lastname: Verdoes
authors.affiliation: Department of Bio-organic Synthesis, Leiden University, Leiden, The Netherlands.
authors.forename: Hermen S
authors.initials: HS
authors.lastname: Overkleeft
authors.affiliation: INSERM U955, Département de Physiologie, Université Paris-Est Créteil (UPEC), Créteil, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Marcos
authors.affiliation: INSERM U955, Département de Physiologie, Université Paris-Est Créteil (UPEC), Créteil, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Adnot
authors.affiliation: Research Unit Protein Science, Helmholtz Zentrum München, Munich, Germany.
authors.forename: Stefanie M
authors.initials: SM
authors.lastname: Hauck
authors.affiliation: Department of Internal Medicine, Justus-Liebig-University Giessen, Universities Giessen &Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Giessen, Germany.
authors.forename: Clemens
authors.initials: C
authors.lastname: Ruppert
authors.affiliation: 1] Department of Internal Medicine, Justus-Liebig-University Giessen, Universities Giessen &Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Giessen, Germany [2] Agaplesion Pneumologische Klinik Waldhof-Elgershausen, Greifenstein, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Günther
authors.affiliation: Department of Internal Medicine II, Section of Infectious Diseases, Justus- Liebig-University, Universities Giessen &Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Giessen, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Herold
authors.affiliation: Research Unit Gene Vectors, Helmholtz Zentrum München, Munich, Germany.
authors.forename: Shinji
authors.initials: S
authors.lastname: Ohno
authors.affiliation: Research Unit Gene Vectors, Helmholtz Zentrum München, Munich, Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: Adler
authors.affiliation: Comprehensive Pneumology Center (CPC), University Hospital, Ludwig-Maximilians University, Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), Munich, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Eickelberg
authors.affiliation: Comprehensive Pneumology Center (CPC), University Hospital, Ludwig-Maximilians University, Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), Munich, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Meiners
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology; D000818:Animals; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism; D005260:Female; D006566:Herpesviridae Infections / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D016676:Macrophages, Alveolar / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology*; D018144:Rhadinovirus / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014412:Tumor Virus Infections / Q000276:immunology
chemical_list: C071313:LMP-2 protein; D007371:Interferon-gamma; D003546:Cysteine Endopeptidases; C077436:LMP7 protein; D046988:Proteasome Endopeptidase Complex