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

Nat Immunol. 2018 Feb;19(2):192-201. doi: 10.1038/s41590-017-0030-x. Epub 2018 Jan 15.

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 CD11bhiL-selectinloCXCR4+ 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • Lung Diseases, Interstitial / immunology
  • Lung Diseases, Interstitial / pathology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neutrophils / pathology*
  • Pulmonary Fibrosis / immunology
  • Pulmonary Fibrosis / pathology*