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

Am. J. Physiol. Lung Cell Mol. Physiol. 307, L692-L706 (2014)
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Open Access Green
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, we demonstrate that B cell-deficient mice are significantly protected against CS-induced emphysema. Chronic CS exposure led to an increased size and number of iBALT structures, and increased lung compliance and mean linear chord length in WT, but not B cell-deficient mice. The increased accumulation of lung resident 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, which could be inhibited by an anti-IL10 antibody. In summary, B cell function in iBALT formation seems necessary for macrophage activation and tissue destruction in CS-induced emphysema, and possibly provides a new target for therapeutic intervention in COPD.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter B Cells ; Copd ; Il-10 ; Ibalt ; Macrophages; Obstructive Pulmonary-disease; Lymphoid-tissue Ibalt; Induced Emphysema; Peripheral Airways; Local Immunity; Mouse Models; Mice; Lung; Neogenesis; Inflammation
ISSN (print) / ISBN 1040-0605
e-ISSN 1522-1504
Quellenangaben Band: 307, Heft: 9, Seiten: L692-L706 Artikelnummer: , Supplement: ,
Verlag American Physiological Society
Verlagsort Bethesda, Md. [u.a.]
Begutachtungsstatus Peer reviewed