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| Status |
Public on Jul 27, 2021 |
| Title |
Alveolar macrophage gene expression in a mouse model of MAS |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Macrophage activation syndrome (MAS) is a life-threatening complication of systemic juvenile idiopathic arthritis (SJIA), and increasingly reported in association with severe lung disease (SJIA-LD) of unknown etiology. This study mechanistically defines the novel observation of pulmonary inflammation in the TLR9 mouse model of MAS that recapitulate key features of SJIA-LD, including IFNg activation. In acute MAS, lungs exhibit a mild but diffuse lymphocyte-predominant perivascular, interstitial inflammation with elevated IFNg, IFN-induced chemokines, and alveolar macrophage (AMf) expression of IFNg-induced genes. However, MAS resolution demonstrated AMf expansion and increased interstitial inflammation. AMf microarrays confirmed IFNg-induced proinflammatory polarization during acute MAS, which switches towards anti-inflammatory phenotype during MAS resolution. Interestingly, recurrent MAS increased alveolar inflammation, and reset polarization towards a pro-inflammatory state. Furthermore, in mice bearing macrophages insensitive to IFNg, both systemic feature of MAS and pulmonary inflammation were markedly attenuated. These findings demonstrate experimental MAS induces IFNg-driven pulmonary inflammation, and define this system for further study of and treatment validation in SJIA-LD.
We used microarrays to study whole transcriptome analysis of alveolar macrophages in the TLR9 mouse model of MAS during both acute MAS and MAS resolution.
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| Overall design |
11 mice were given 5 injections over 10 days with vehicle (PBS) or CpG. BAL fluid was obtained on day 10 (acute MAS) or day 30 (MAS resolution). Alveolar macrophages were purified by adherence, and RNA extraction for hybridization on Affymetrix microarrays.
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| Contributor(s) |
Gao DK, Salomonis N, Henderlight M, Woods C, Thakkar K, Grom AA, Thornton S, Jordan MB, Wikenheiser-Brokamp KA, Schulert GS |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Apr 21, 2020 |
| Last update date |
Jul 29, 2021 |
| Contact name |
Denny Kan Gao |
| E-mail(s) |
Denny.Gao@cchmc.org
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| Organization name |
Cincinnati Children's Hospital Medical Center
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| Department |
Rheumatology
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| Lab |
Schulert
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| Street address |
3333 Burnet Avenue
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| City |
Cincinnati |
| State/province |
OH |
| ZIP/Postal code |
45229 |
| Country |
USA |
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| Platforms (1) |
| GPL23038 |
[Clariom_S_Mouse] Affymetrix Clariom S Assay, Mouse (Includes Pico Assay) |
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| Samples (11)
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| GSM4487801 |
Control macrophages, biological replicate 1 |
| GSM4487802 |
Control macrophages, biological replicate 2 |
| GSM4487803 |
Control macrophages, biological replicate 3 |
| GSM4487804 |
Control macrophages, biological replicate 4 |
| GSM4487805 |
Acute MAS macrophages, biological replicate 1 |
| GSM4487806 |
Acute MAS macrophages, biological replicate 2 |
| GSM4487807 |
Acute MAS macrophages, biological replicate 3 |
| GSM4487808 |
MAS resolution macrophages, biological replicate 1 |
| GSM4487809 |
MAS resolution macrophages, biological replicate 2 |
| GSM4487810 |
MAS resolution macrophages, biological replicate 3 |
| GSM4487811 |
MAS resolution macrophages, biological replicate 4 |
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| Relations |
| BioProject |
PRJNA627190 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE149034_RAW.tar |
12.8 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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