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Series GSE198768 Query DataSets for GSE198768
Status Public on Apr 03, 2022
Title Genome-wide epigenome mapping in alveolar macrophages (CD45+ Siclec F+ CD11c+) from WT (4wks and 12 wks) and CGD (4wks and 12 wks) mice
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary The leukocyte NADPH oxidase 2 (NOX2) plays a key role in pathogen killing and immunoregulation. Genetic defects in NOX2 result in chronic granulomatous disease (CGD), associated with microbial infections and inflammatory disorders, often involving the lung. Alveolar macrophages (AM) are the predominant immune cell in the airways at steady state, and limiting their activation is important given constant exposure to inhaled materials, yet the importance of NOX2 in this process is not well-understood. Here, we show a previously undescribed role for NOX2 in maintaining lung homeostasis by suppressing AM activation, as studied using CGD mice or mice with selective loss of NOX2 primarily in macrophages. AM lacking NOX2 have increased cytokine responses to TLR2 and TLR4 stimulation ex vivo. Moreover, between 4 and 12 weeks of age, mice with global NOX2 deletion developed an activated CD11bhigh subset of AM with epigenetic and transcriptional profiles reflecting immune activation compared to WT AM. The presence of CD11bhigh AM in CGD mice correlated with increased numbers of alveolar neutrophils and proinflammatory cytokines at steady state as well as increased lung inflammation following insults. Moreover, deletion of NOX2 primarily in macrophages was sufficient for mice to develop an activated CD11bhigh AM subset and accompanying pro-inflammatory sequela. Additionally, we showed that the altered resident macrophage transcriptional profile in the absence of NOX2 is tissue-specific as these changes were not seen in resident peritoneal macrophages. Thus, these data demonstrate that absence of NOX2 in alveolar macrophages leads to their pro-inflammatory remodeling and dysregulates alveolar homeostasis.
Overall design Alveolar macrophage subsets were isolated from WT and CGD mice at the stated ages for ATAC seq.
Contributor(s) Bhattacharya S, Yang W, Li Y, Magee JA, Dinauer MC
Citation(s) 35357446
Submission date Mar 16, 2022
Last update date Apr 03, 2022
Contact name Mary C Dinauer
Organization name Washington University In St Louis
Department Pathology & Immunology
Street address 660 South Euclid Ave
City St Louis
State/province Missouri
ZIP/Postal code 63110
Country USA
Platforms (1)
GPL21493 Illumina HiSeq 3000 (Mus musculus)
Samples (15)
GSM5956518 A
GSM5956519 B
GSM5956520 C
This SubSeries is part of SuperSeries:
GSE198778 The leukocyte NADPH oxidase 2 (NOX2) plays a key role in pathogen killing and immunoregulation
BioProject PRJNA816852

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Supplementary file Size Download File type/resource
GSE198768_CGD_hi_12wk.fc.signal.bigwig 366.1 Mb (ftp)(http) BIGWIG
GSE198768_CGD_hi_12wk.narrowPeak.gz 1.9 Mb (ftp)(http) NARROWPEAK
GSE198768_CGD_lo_12wk.fc.signal.bigwig 374.8 Mb (ftp)(http) BIGWIG
GSE198768_CGD_lo_12wk.narrowPeak.gz 1.7 Mb (ftp)(http) NARROWPEAK
GSE198768_CGD_lo_4wk.fc.signal.bigwig 428.0 Mb (ftp)(http) BIGWIG
GSE198768_CGD_lo_4wk.narrowPeak.gz 1.9 Mb (ftp)(http) NARROWPEAK
GSE198768_WT_lo_12wk.fc.signal.bigwig 426.6 Mb (ftp)(http) BIGWIG
GSE198768_WT_lo_12wk.narrowPeak.gz 1.5 Mb (ftp)(http) NARROWPEAK
GSE198768_WT_lo_4wk.fc.signal.bigwig 403.1 Mb (ftp)(http) BIGWIG
GSE198768_WT_lo_4wk.narrowPeak.gz 1.5 Mb (ftp)(http) NARROWPEAK
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