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2015 ; 5
(ä): 10230
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Regulation of immunoproteasome function in the lung
#MMPMID25989070
Keller IE
; Vosyka O
; Takenaka S
; Kloß A
; Dahlmann B
; Willems LI
; Verdoes M
; Overkleeft HS
; Marcos E
; Adnot S
; Hauck SM
; Ruppert C
; Günther A
; Herold S
; Ohno S
; Adler H
; Eickelberg O
; Meiners S
Sci Rep
2015[May]; 5
(ä): 10230
PMID25989070
show ga
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
IFN? 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.
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