Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Cigarette smoke-induced iBALT mediates macrophage activation in a B cell-dependent manner in COPD

ABSTRACT: 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. Expression data of mice treated with cigarette smoke. Lung tissue was analysed at four and six months of age.

ORGANISM(S): Mus musculus

SUBMITTER: Johannes Beckers

PROVIDER: E-GEOD-52509 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Cigarette smoke-induced iBALT mediates macrophage activation in a B cell-dependent manner in COPD.

John-Schuster Gerrit G Hager Katrin K Conlon Thomas M TM Irmler Martin M Beckers Johannes J Eickelberg Oliver O Yildirim Ali Önder AÖ

American journal of physiology. Lung cellular and molecular physiology 20140815 9

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 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 and macrophages accumulate in the lungs and contribute to CS-induced emphysema, but the mechanisms thereof remain unclear. Here, w ...[more]

PMID: 25128521

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Dataset Information

Cigarette smoke-induced iBALT mediates macrophage activation in a B cell-dependent manner in COPD

Publications

Cigarette smoke-induced iBALT mediates macrophage activation in a B cell-dependent manner in COPD.

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