Aged polymorphonuclear leukocytes cause fibrotic interstitial lung disease in the absence of regulation by B cells

作者：Kim Jung Hwan; Podstawka John; Lou Yuefei; Li Lu; Lee Esther K S; Divangahi Maziar; Petri Bjorn; Jirik Frank R; Kelly Margaret M; Yipp Bryan G^*

来源：Nature Immunology, 2018, 19(2): 192-+.

DOI：10.1038/s41590-017-0030-x

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-selectin(lo)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 beta(2) 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.

• 出版日期2018-2
• 单位McGill