Cell
Volume 169, Issue 3, 20 April 2017, Pages 497-509.e13
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Article
Spontaneous Chitin Accumulation in Airways and Age-Related Fibrotic Lung Disease

https://doi.org/10.1016/j.cell.2017.03.044Get rights and content
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Highlights

  • AMCase-expressing epithelial cells mediate endochitinase activity in the airways

  • Environmental chitin spontaneously accumulates in airways lacking AMCase

  • Persistent immune activation and age-related fibrosis develop in the absence of AMCase

  • Mice with fibrotic lung disease and humans with ILD accumulate chitin in airways

Summary

The environmentally widespread polysaccharide chitin is degraded and recycled by ubiquitous bacterial and fungal chitinases. Although vertebrates express active chitinases from evolutionarily conserved loci, their role in mammalian physiology is unclear. We show that distinct lung epithelial cells secrete acidic mammalian chitinase (AMCase), which is required for airway chitinase activity. AMCase-deficient mice exhibit premature morbidity and mortality, concomitant with accumulation of environmentally derived chitin polymers in the airways and expression of pro-fibrotic cytokines. Over time, these mice develop spontaneous pulmonary fibrosis, which is ameliorated by restoration of lung chitinase activity by genetic or therapeutic approaches. AMCase-deficient epithelial cells express fibrosis-associated gene sets linked with cell stress pathways. Mice with lung fibrosis due to telomere dysfunction and humans with interstitial lung disease also accumulate excess chitin polymers in their airways. These data suggest that altered chitin clearance could exacerbate fibrogenic pathways in the setting of lung diseases characterized by epithelial cell dysfunction.

Keywords

AMCase
chitin
chitinase
epithelium
pulmonary fibrosis
interleukins
interstitial lung disease
age-related disease
polysaccharide

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