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| Status |
Public on Mar 26, 2019 |
| Title |
The lung environment controls alveolar macrophage metabolism and responsiveness during type-2 inflammation. |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Fine control of macrophage activation is required to prevent inflammatory disease, particularly at barrier sites such as the lung. However, the dominant mechanisms that regulate pulmonary MΦs during inflammation are currently poorly understood. Here we show that airway MΦs are substantially less able to respond to the canonical type-2 cytokine IL-4, which underpins allergic disease and parasite worm infections, than lung tissue or peritoneal cavity MΦs. We reveal that MΦ hypo-responsiveness to IL-4 is dictated by the lung environment, though independent of the host microbiota or the prominent lung extracellular matrix components surfactant protein D and mucin 5b. Rather, compared to cavity MΦs, airway MΦs display severely dysregulated metabolism. Strikingly, upon removal from the lung, alveolar MΦs regain IL-4 responsiveness in a process dependent upon glycolysis. Thus, we propose that impaired glycolysis within the pulmonary niche is a central determinant for regulation of MΦ responsiveness during type-2 inflammation.
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| Overall design |
The 13 analysed samples belong to 6 different groups, each group consisted of 2 or 3 samples. The groups consist of 3 separate macrophage populations, from either control or IL-4 complex treated mice. Each individual sample was generated from 3-5 pooled biological replicate mice.
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| Contributor(s) |
Svedberg F, Cook PC, Macdonald A, Ivens AC |
| Citation(s) |
30936493 |
| |
| Submission date |
Feb 08, 2019 |
| Last update date |
Jun 25, 2019 |
| Contact name |
Alasdair Ivens |
| E-mail(s) |
al.ivens@ed.ac.uk
|
| Phone |
44 131 6513605
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| Organization name |
Centre for Immunity, Infection and Evolution
|
| Street address |
Kings Buildings
|
| City |
Edinburgh |
| ZIP/Postal code |
EH9 3FL |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (13)
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| Relations |
| BioProject |
PRJNA521523 |
| SRA |
SRP184711 |
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