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Series GSE72000 Query DataSets for GSE72000
Status Public on Jun 29, 2016
Title Immunoproteasome dysfunction augments alternative polarization of alveolar macrophages
Organism Mus musculus
Experiment type Expression profiling by array
Summary The proteasome is a central regulatory hub for intracellular signaling by degrading numerous signaling mediators. Immunoproteasomes are specialized types of proteasomes known to be involved in shaping adaptive immune responses, but their role for innate immune signaling is elusive. Here, we analyzed immunoproteasome function for polarization of alveolar macrophages which are highly specialized tissue macrophages of the alveolar surface of the lung.
Classical activation (M1 polarization) of primary alveolar macrophages by LPS/IFNγ transcriptionally induced all three immunoproteasome subunits LMP2, LMP7, and MECL-1. In contrast, IL-4 triggered alternative (M2) activation was accompanied by posttranscriptional upregulation of LMP2 and LMP7. Accordingly, immunoproteasome activity increased in M1 cells, and to some extent under M2 conditions. Analyzing the polarization capability from LMP7 deficient mice revealed no effect on the LPS/IFNγ triggered M1 profile, but uncovered a distorted M2 profile for IL-4 stimulated LMP7-/- alveolar macrophages as characterized by increased M2 marker gene expression and CCL17 cytokine release. This shift in immunoproteasome-dependent M2 polarization was accompanied by amplified AKT/STAT6 activation and IRF4 expression in LMP7-/- alveolar macrophages. IL-13 stimulation of LMP7 deficient cells induced a similar M2 skewed profile and IL4Rα protein expression was generally elevated in LMP7-/- alveolar macrophages, indicating that amplified IL4R signaling in immunoproteasome defective cells may contribute to augmented M2 polarization. Importantly, treatment with an LMP7-specific proteasome inhibitor recapitulated the findings of genetic LMP7 inactivation. Our results thus suggest a novel role of immunoproteasome function for regulating innate immune function of macrophages by limiting IL4R expression and signaling.
 
Overall design Expression data of M0 and M2 macrophages derived from Lmp7 k.o. and control animals
 
Contributor(s) Chen S, Kammerl IE, Vosyka O, Baumann T, Yu Y, Wu Y, Irmler M, Overkleeft HS, Beckers J, Eickelberg O, Meiners S, Stoeger T
Citation(s) 26990663
Submission date Aug 12, 2015
Last update date Jun 14, 2018
Contact name Johannes Beckers
E-mail(s) beckers@helmholtz-muenchen.de
Organization name Helmholtz Zentrum Muenchen
Department Institute of Experimental Genetics
Street address Ingolstaedter Landstr. 1
City Neuherberg
ZIP/Postal code 85764
Country Germany
 
Platforms (1)
GPL6885 Illumina MouseRef-8 v2.0 expression beadchip
Samples (12)
GSM1849536 Macrophage_M0_Lmp7ko_rep1
GSM1849537 Macrophage_M0_Lmp7ko_rep2
GSM1849538 Macrophage_M0_Lmp7ko_rep3
Relations
BioProject PRJNA292698

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE72000_RAW.tar 3.1 Mb (http)(custom) TAR
GSE72000_non-normalized.txt.gz 1.0 Mb (ftp)(http) TXT
Raw data are available on Series record
Processed data included within Sample table

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