Innate Lymphoid Cell-Dependent Airway Epithelial and Inflammatory Responses to Inhaled Ozone: A New Paradigm in Pathogenesis

Toxicol Pathol. 2019 Dec;47(8):993-1003. doi: 10.1177/0192623319873872. Epub 2019 Sep 19.

Abstract

Epidemiological associations have been made between the new onset of childhood rhinitis/asthma and exposures to elevated ambient levels of ozone, a commonly encountered gaseous air pollutant. Our laboratory was the first to find that mice repeatedly exposed to ozone develop nasal type 2 immunity and eosinophilic rhinitis with mucous cell metaplasia. More recently, we have found that these ozone-induced upper airway alterations are mediated by group 2 innate lymphoid cells (ILC2s) and not by T and B cells that are important in adaptive immune responses typically associated with allergic rhinitis and asthma. Furthermore, repeated exposures of mice to ozone cause ILC2-mediated type 2 immunity and airway pathology in the lungs, like those found in the nasal airways. Our recent findings in ozone-exposed mice complement and extend previous reports of nonallergic nasal airway disease in ozone-exposed rats and nonhuman primates. Overall, these experimental results in laboratory animals suggest a plausible ILC2-dependent paradigm for the toxicologic pathobiology that underlies the development of nonallergic rhinitis/asthma in children who live in environments with repeated occurrences of high ambient concentrations of ozone.

Keywords: eosinophils; innate lymphoid cells; mice; monkeys; mucous cell metaplasia; nonallergic rhinitis and asthma; ozone; rats.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Air Pollutants / toxicity*
  • Animals
  • Humans
  • Immunity, Innate / drug effects*
  • Inhalation Exposure / adverse effects*
  • Lymphocytes / drug effects*
  • Lymphocytes / immunology
  • Lymphocytes / pathology
  • Metaplasia
  • Ozone / toxicity*
  • Respiratory Mucosa / drug effects*
  • Respiratory Mucosa / immunology
  • Respiratory Mucosa / pathology
  • Respiratory Tract Diseases / chemically induced
  • Respiratory Tract Diseases / immunology
  • Respiratory Tract Diseases / pathology
  • Species Specificity

Substances

  • Air Pollutants
  • Ozone