Innate Lymphoid Cells Mediate Pulmonary Eosinophilic Inflammation, Airway Mucous Cell Metaplasia, and Type 2 Immunity in Mice Exposed to Ozone

Kazuyoshi Kumagai, Ryan P. Lewandowski, Daven N. Jackson-Humbles, Nicholas Buglak, Ning Li, Kaylin White, Steven J. Van Dyken, James G. Wagner, Jack R. Harkema

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Exposure to elevated levels of ambient ozone in photochemical smog is associated with eosinophilic airway inflammation and nonatopic asthma in children. In the present study, we determined the role of innate lymphoid cells (ILCs) in the pathogenesis of ozone-induced nonatopic asthma by using lymphoid cell-sufficient C57BL/6 mice, ILC-sufficient Rag2-/- mice (devoid of T and B cells), and ILC-deficient Rag2-/-Il2rg-/- mice (depleted of all lymphoid cells including ILCs). Mice were exposed to 0 or 0.8 parts per million ozone for 1 day or 9 consecutive weekdays (4 hr/day). A single exposure to ozone caused neutrophilic inflammation, airway epithelial injury, and reparative DNA synthesis in all strains of mice, irrespective of the presence or absence of ILCs. In contrast, 9-day exposures induced eosinophilic inflammation and mucous cell metaplasia only in the lungs of ILC-sufficient mice. Repeated ozone exposures also elicited increased messenger RNA expression of transcripts associated with type 2 immunity and airway mucus production in ILC-sufficient mice. ILC-deficient mice repeatedly exposed to ozone had no pulmonary pathology or increased gene expression related to type 2 immunity. These results suggest a new paradigm for the biologic mechanisms underlying the development of a phenotype of childhood nonatopic asthma that has been linked to ambient ozone exposures.

Original languageEnglish
Pages (from-to)692-704
Number of pages13
JournalToxicologic Pathology
Volume45
Issue number6
DOIs
StatePublished - Aug 1 2017

Keywords

  • eosinophilic inflammation
  • innate lymphoid cells
  • lung
  • mice
  • mucous cell metaplasia
  • ozone
  • type 2 immunity

Fingerprint

Dive into the research topics of 'Innate Lymphoid Cells Mediate Pulmonary Eosinophilic Inflammation, Airway Mucous Cell Metaplasia, and Type 2 Immunity in Mice Exposed to Ozone'. Together they form a unique fingerprint.

Cite this