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| Status |
Public on Dec 04, 2014 |
| Title |
Cigarette smoke-induced iBALT mediates macrophage activation in a B cell-dependent manner in COPD |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Chronic obstructive pulmonary disease (COPD) is characterized by a progressive decline in lung function, caused by exposure to exogenous particles, mainly cigarette smoke (CS). COPD pathogenesis is initiated and perpetuated by an abnormal CS-induced inflammatory response of the lungs, involving both innate and adaptive immunity. Specifically, B cells organized in iBALT structures, as well as macrophages, accumulate in the lungs and contribute to CS-induced emphysema, but the mechanisms thereof remain unclear.
Here, we demonstrate that B cell-deficient mice are significantly protected against CS-induced emphysema. Chronic CS exposure led to increased lung compliance, total lung capacity, and mean linear chord length in WT, but not B cell-deficient mice, associated with an increased size and number of iBALT structures. The increased accumulation of macrophages around iBALT and in emphysematous alveolar areas in CS-exposed WT mice coincided with upregulated MMP12 expression. In vitro co-culture experiments using B cells and macrophages demonstrated that B cell-derived IL-10 drives macrophage activation and MMP12 upregulation. In summary, B cell function in iBALT formation in CS-induced emphysema provides a new innovative mechanism, which could be explored as a target for therapeutic intervention in COPD patients.
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| Overall design |
Expression data of mice treated with cigarette smoke. Lung tissue was analysed at four and six months of age.
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| Contributor(s) |
John-Schuster G, Hager K, Irmler M, Beckers J, Conlon TM, Eickelberg O, Yildirim AO |
| Citation(s) |
25128521 |
| Submission date |
Nov 19, 2013 |
| Last update date |
Jun 14, 2018 |
| Contact name |
Johannes Beckers |
| E-mail(s) |
johannes.beckers@helmholtz-munich.de
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| Organization name |
Helmholtz Zentrum Muenchen
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| Department |
Institute of Experimental Genetics
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| Street address |
Ingolstaedter Landstr. 1
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| City |
Neuherberg |
| ZIP/Postal code |
85764 |
| Country |
Germany |
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| Platforms (1) |
| GPL6885 |
Illumina MouseRef-8 v2.0 expression beadchip |
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| Samples (12)
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| GSM1267994 |
Lung tissue from cigarette smoke-treated mice at 4 months of age, biological replicate 1 |
| GSM1267995 |
Lung tissue from cigarette smoke-treated mice at 4 months of age, biological replicate 2 |
| GSM1267996 |
Lung tissue from cigarette smoke-treated mice at 4 months of age, biological replicate 3 |
| GSM1267997 |
Lung tissue from control mice at 4 months of age, biological replicate 1 |
| GSM1267998 |
Lung tissue from control mice at 4 months of age, biological replicate 2 |
| GSM1267999 |
Lung tissue from control mice at 4 months of age, biological replicate 3 |
| GSM1268000 |
Lung tissue from cigarette smoke-treated mice at 6 months of age, biological replicate 1 |
| GSM1268001 |
Lung tissue from cigarette smoke-treated mice at 6 months of age, biological replicate 2 |
| GSM1268002 |
Lung tissue from cigarette smoke-treated mice at 6 months of age, biological replicate 3 |
| GSM1268003 |
Lung tissue from control mice at 6 months of age, biological replicate 1 |
| GSM1268004 |
Lung tissue from control mice at 6 months of age, biological replicate 2 |
| GSM1268005 |
Lung tissue from control mice at 6 months of age, biological replicate 3 |
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| Relations |
| BioProject |
PRJNA229140 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE52509_RAW.tar |
3.1 Mb |
(http)(custom) |
TAR |
| GSE52509_non-normalized.txt.gz |
947.8 Kb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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