1. Aged polymorphonuclear leukocytes cause fibrotic interstitial lung disease in the absence of regulation by B cells.
- Author
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Kim JH, Podstawka J, Lou Y, Li L, Lee EKS, Divangahi M, Petri B, Jirik FR, Kelly MM, and Yipp BG
- Subjects
- Animals, Lung Diseases, Interstitial immunology, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Pulmonary Fibrosis immunology, B-Lymphocytes immunology, Lung Diseases, Interstitial pathology, Neutrophils pathology, Pulmonary Fibrosis pathology
- Abstract
Pulmonary immunity requires tight regulation, as interstitial inflammation can compromise gas exchange and lead to respiratory failure. Here we found a greater number of aged CD11b
hi L-selectinlo CXCR4+ polymorphonuclear leukocytes (PMNs) in lung vasculature than in the peripheral circulation. Using pulmonary intravital microscopy, we observed lung PMNs physically interacting with B cells via β2 integrins; this initiated neutrophil apoptosis, which led to macrophage-mediated clearance. Genetic deletion of B cells led to the accumulation of aged PMNs in the lungs without systemic inflammation, which caused pathological fibrotic interstitial lung disease that was attenuated by the adoptive transfer of B cells or depletion of PMNs. Thus, the lungs are an intermediary niche in the PMN lifecycle wherein aged PMNs are regulated by B cells, which restrains their potential to cause pulmonary pathology.- Published
- 2018
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