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| 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
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| 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.
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| Overall design |
Alveolar macrophage subsets were isolated from WT and CGD mice at the stated ages for ATAC seq.
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| 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 |
| E-mail(s) |
mdinauer@wustl.edu
|
| 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 |
| |
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| Platforms (1) |
| GPL21493 |
Illumina HiSeq 3000 (Mus musculus) |
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| Samples (15)
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| This SubSeries is part of SuperSeries: |
| GSE198778 |
The leukocyte NADPH oxidase 2 (NOX2) plays a key role in pathogen killing and immunoregulation |
|
| Relations |
| BioProject |
PRJNA816852 |
| 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 |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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