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

4 Citations (Scopus)

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

Fingerprint

Interleukins
Primates
Epithelial Cells
Lung
trichostatin A
Epithelium
Deoxycytidine
Macaca mulatta
interleukin-22 receptor
Child Mortality
Messenger RNA
Proteins
Histone Deacetylases
Methyltransferases
Pathogens
Cell culture
Epigenomics
Respiratory Tract Infections
Haplorhini
Fluorescent Antibody Technique

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

Cite this

Attenuated airway epithelial cell interleukin-22R1 expression in the infant nonhuman primate lung. / Dugger, Daniel T.; Gerriets, Joan E.; Miller, Lisa.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 53, No. 6, 01.12.2015, p. 761-768.

Research output: Contribution to journalArticle

@article{e2f0908117af456588bcade9b44e01aa,
title = "Attenuated airway epithelial cell interleukin-22R1 expression in the infant nonhuman primate lung",
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.",
keywords = "Epigenetic, Innate immunity, Primate, Respiratory development, Trichostatin a",
author = "Dugger, {Daniel T.} and Gerriets, {Joan E.} and Lisa Miller",
year = "2015",
month = "12",
day = "1",
doi = "10.1165/rcmb.2014-0452RC",
language = "English (US)",
volume = "53",
pages = "761--768",
journal = "American Journal of Respiratory Cell and Molecular Biology",
issn = "1044-1549",
publisher = "American Thoracic Society",
number = "6",

}

TY - JOUR

T1 - Attenuated airway epithelial cell interleukin-22R1 expression in the infant nonhuman primate lung

AU - Dugger, Daniel T.

AU - Gerriets, Joan E.

AU - Miller, Lisa

PY - 2015/12/1

Y1 - 2015/12/1

N2 - 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.

AB - 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.

KW - Epigenetic

KW - Innate immunity

KW - Primate

KW - Respiratory development

KW - Trichostatin a

UR - http://www.scopus.com/inward/record.url?scp=84963830298&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84963830298&partnerID=8YFLogxK

U2 - 10.1165/rcmb.2014-0452RC

DO - 10.1165/rcmb.2014-0452RC

M3 - Article

VL - 53

SP - 761

EP - 768

JO - American Journal of Respiratory Cell and Molecular Biology

JF - American Journal of Respiratory Cell and Molecular Biology

SN - 1044-1549

IS - 6

ER -