Attenuated airway epithelial cell interleukin-22R1 expression in the infant nonhuman primate lung

Daniel T. Dugger, Joan E. Gerriets, Lisa Miller

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Respiratory tract infections are a leading cause of morbidity and mortality in children under 5 years of age. Increased susceptibility to infection is associated with deficiencies in immunity during early childhood. Airway epithelium represents the first line of mucosal defense against inhaled pathogens. However, little is known about epithelial immune mechanisms in the maturing lung. IL-22 and its receptor IL-22R1 are important in host defense and repair of epithelial barriers. The objective of this study was to determine whether a quantitative difference in IL-22R1 exists between infant and adult airways using the rhesus macaque monkey as a model of childhood lung development. Immunofluorescence staining of tracheal tissue revealed minimal expression of IL-22R1 in epithelium at 1 month of age, with a progressive increase in fluorescence-positive basal cells through 1 year of age. Western blot analysis of tracheal lysates confirmed significant age-dependent differences in IL-22R1 protein content. Further, primary tracheobronchial epithelial cell cultures established from infant and adult monkeys showed differential IL-22R1mRNA and protein expression in vitro. To begin to assess the regulation of age-dependent IL-22R1 expression in airway epithelium, the effect of histone deacetylase and DNA methyltransferase inhibitors was evaluated. IL-22R1 mRNA in adult cultures was not altered by 5-aza-29-deoxycytidine or trichostatin A. IL-22R1 mRNA in infant cultures showed no change with 5-aza-29-deoxycytidine but was significantly increased after trichostatin A treatment; however, IL-22R1 protein did not increase concurrently. These data suggest that IL-22R1 in airway epithelium is regulated, in part, by epigenetic mechanisms that are dependent on chronologic age.

Original languageEnglish (US)
Pages (from-to)761-768
Number of pages8
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume53
Issue number6
DOIs
StatePublished - Dec 1 2015

Keywords

  • Epigenetic
  • Innate immunity
  • Primate
  • Respiratory development
  • Trichostatin a

ASJC Scopus subject areas

  • Medicine(all)
  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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