Mucosal production of uric acid by airway epithelial cells contributes to particulate matter-induced allergic sensitization

Mucosal Immunol. 2016 May;9(3):809-20. doi: 10.1038/mi.2015.104. Epub 2015 Oct 28.


Exposure to particulate matter (PM), a major component of air pollution, contributes to increased morbidity and mortality worldwide. PM induces innate immune responses and contributes to allergic sensitization, although the mechanisms governing this process remain unclear. Lung mucosal uric acid has also been linked to allergic sensitization. The links among PM exposure, uric acid, and allergic sensitization remain unexplored. We therefore investigated the mechanisms behind PM-induced allergic sensitization in the context of lung mucosal uric acid. PM10 and house dust mite exposure selectively induced lung mucosal uric acid production and secretion in vivo, which did not occur with other challenges (lipopolysaccharide, virus, bacteria, or inflammatory/fibrotic stimuli). PM10-induced uric acid mediates allergic sensitization and augments antigen-specific T-cell proliferation, which is inhibited by uricase. We then demonstrate that human airway epithelial cells secrete uric acid basally and after stimulation through a previously unidentified mucosal secretion system. Our work discovers a previously unknown mechanism of air pollution-induced, uric acid-mediated, allergic sensitization that may be important in the pathogenesis of asthma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Dermatophagoides / immunology*
  • Cell Proliferation
  • Cells, Cultured
  • Environmental Exposure / adverse effects
  • Female
  • Humans
  • Hypersensitivity / immunology*
  • Immunity, Mucosal
  • Immunization
  • Lung / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Particulate Matter / immunology*
  • Pyroglyphidae
  • Respiratory Mucosa / immunology*
  • Respiratory Mucosa / pathology
  • T-Lymphocytes / immunology*
  • Toll-Like Receptor 4 / genetics
  • Uric Acid / metabolism*


  • Antigens, Dermatophagoides
  • Particulate Matter
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • Uric Acid

Grant support