Neonatal hyperoxia promotes asthma-like features through IL-33-dependent ILC2 responses

In Su Cheon, Young Min Son, Li Jiang, Nicholas P. Goplen, Mark Kaplan, Andrew H. Limper, Hirohito Kita, Sophie Paczesny, Y. S. Prakash, Robert Tepper, Shawn K. Ahlfeld, Jie Sun

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background: Premature infants often require oxygen supplementation and, therefore, are exposed to oxidative stress. Following oxygen exposure, preterm infants frequently develop chronic lung disease and have a significantly increased risk of asthma. Objective: We sought to identify the underlying mechanisms by which neonatal hyperoxia promotes asthma development. Methods: Mice were exposed to neonatal hyperoxia followed by a period of room air recovery. A group of mice was also intranasally exposed to house dust mite antigen. Assessments were performed at various time points for evaluation of airway hyperresponsiveness, eosinophilia, mucus production, inflammatory gene expression, and TH and group 2 innate lymphoid cell (ILC2) responses. Sera from term- and preterm-born infants were also collected and levels of IL-33 and type 2 cytokines were measured. Results: Neonatal hyperoxia induced asthma-like features including airway hyperresponsiveness, mucus hyperplasia, airway eosinophilia, and type 2 pulmonary inflammation. In addition, neonatal hyperoxia promoted allergic TH responses to house dust mite exposure. Elevated IL-33 levels and ILC2 responses were observed in the lungs most likely due to oxidative stress caused by neonatal hyperoxia. IL-33 receptor signaling and ILC2s were vital for the induction of asthma-like features following neonatal hyperoxia. Serum IL-33 levels correlated significantly with serum levels of IL-5 and IL-13 but not IL-4 in preterm infants. Conclusions: These data demonstrate that an axis involving IL-33 and ILC2s is important for the development of asthma-like features following neonatal hyperoxia and suggest therapeutic potential for targeting IL-33, ILC2s, and oxidative stress to prevent and/or treat asthma development related to prematurity.

Original languageEnglish (US)
JournalJournal of Allergy and Clinical Immunology
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Hyperoxia
Asthma
Premature Infants
Oxidative Stress
Eosinophilia
Mucus
Serum
Oxygen
Dermatophagoides Antigens
Recovery Room
Pyroglyphidae
Interleukin-13
Interleukin-5
Interleukin-33
Interleukin-4
Lung Diseases
Hyperplasia
Interleukin-2
Pneumonia
Chronic Disease

Keywords

  • Asthma
  • IL-33
  • ILC2s
  • Neonatal hyperoxia
  • Oxidative stress

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Neonatal hyperoxia promotes asthma-like features through IL-33-dependent ILC2 responses. / Cheon, In Su; Son, Young Min; Jiang, Li; Goplen, Nicholas P.; Kaplan, Mark; Limper, Andrew H.; Kita, Hirohito; Paczesny, Sophie; Prakash, Y. S.; Tepper, Robert; Ahlfeld, Shawn K.; Sun, Jie.

In: Journal of Allergy and Clinical Immunology, 01.01.2018.

Research output: Contribution to journalArticle

Cheon, In Su ; Son, Young Min ; Jiang, Li ; Goplen, Nicholas P. ; Kaplan, Mark ; Limper, Andrew H. ; Kita, Hirohito ; Paczesny, Sophie ; Prakash, Y. S. ; Tepper, Robert ; Ahlfeld, Shawn K. ; Sun, Jie. / Neonatal hyperoxia promotes asthma-like features through IL-33-dependent ILC2 responses. In: Journal of Allergy and Clinical Immunology. 2018.
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abstract = "Background: Premature infants often require oxygen supplementation and, therefore, are exposed to oxidative stress. Following oxygen exposure, preterm infants frequently develop chronic lung disease and have a significantly increased risk of asthma. Objective: We sought to identify the underlying mechanisms by which neonatal hyperoxia promotes asthma development. Methods: Mice were exposed to neonatal hyperoxia followed by a period of room air recovery. A group of mice was also intranasally exposed to house dust mite antigen. Assessments were performed at various time points for evaluation of airway hyperresponsiveness, eosinophilia, mucus production, inflammatory gene expression, and TH and group 2 innate lymphoid cell (ILC2) responses. Sera from term- and preterm-born infants were also collected and levels of IL-33 and type 2 cytokines were measured. Results: Neonatal hyperoxia induced asthma-like features including airway hyperresponsiveness, mucus hyperplasia, airway eosinophilia, and type 2 pulmonary inflammation. In addition, neonatal hyperoxia promoted allergic TH responses to house dust mite exposure. Elevated IL-33 levels and ILC2 responses were observed in the lungs most likely due to oxidative stress caused by neonatal hyperoxia. IL-33 receptor signaling and ILC2s were vital for the induction of asthma-like features following neonatal hyperoxia. Serum IL-33 levels correlated significantly with serum levels of IL-5 and IL-13 but not IL-4 in preterm infants. Conclusions: These data demonstrate that an axis involving IL-33 and ILC2s is important for the development of asthma-like features following neonatal hyperoxia and suggest therapeutic potential for targeting IL-33, ILC2s, and oxidative stress to prevent and/or treat asthma development related to prematurity.",
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AU - Cheon, In Su

AU - Son, Young Min

AU - Jiang, Li

AU - Goplen, Nicholas P.

AU - Kaplan, Mark

AU - Limper, Andrew H.

AU - Kita, Hirohito

AU - Paczesny, Sophie

AU - Prakash, Y. S.

AU - Tepper, Robert

AU - Ahlfeld, Shawn K.

AU - Sun, Jie

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background: Premature infants often require oxygen supplementation and, therefore, are exposed to oxidative stress. Following oxygen exposure, preterm infants frequently develop chronic lung disease and have a significantly increased risk of asthma. Objective: We sought to identify the underlying mechanisms by which neonatal hyperoxia promotes asthma development. Methods: Mice were exposed to neonatal hyperoxia followed by a period of room air recovery. A group of mice was also intranasally exposed to house dust mite antigen. Assessments were performed at various time points for evaluation of airway hyperresponsiveness, eosinophilia, mucus production, inflammatory gene expression, and TH and group 2 innate lymphoid cell (ILC2) responses. Sera from term- and preterm-born infants were also collected and levels of IL-33 and type 2 cytokines were measured. Results: Neonatal hyperoxia induced asthma-like features including airway hyperresponsiveness, mucus hyperplasia, airway eosinophilia, and type 2 pulmonary inflammation. In addition, neonatal hyperoxia promoted allergic TH responses to house dust mite exposure. Elevated IL-33 levels and ILC2 responses were observed in the lungs most likely due to oxidative stress caused by neonatal hyperoxia. IL-33 receptor signaling and ILC2s were vital for the induction of asthma-like features following neonatal hyperoxia. Serum IL-33 levels correlated significantly with serum levels of IL-5 and IL-13 but not IL-4 in preterm infants. Conclusions: These data demonstrate that an axis involving IL-33 and ILC2s is important for the development of asthma-like features following neonatal hyperoxia and suggest therapeutic potential for targeting IL-33, ILC2s, and oxidative stress to prevent and/or treat asthma development related to prematurity.

AB - Background: Premature infants often require oxygen supplementation and, therefore, are exposed to oxidative stress. Following oxygen exposure, preterm infants frequently develop chronic lung disease and have a significantly increased risk of asthma. Objective: We sought to identify the underlying mechanisms by which neonatal hyperoxia promotes asthma development. Methods: Mice were exposed to neonatal hyperoxia followed by a period of room air recovery. A group of mice was also intranasally exposed to house dust mite antigen. Assessments were performed at various time points for evaluation of airway hyperresponsiveness, eosinophilia, mucus production, inflammatory gene expression, and TH and group 2 innate lymphoid cell (ILC2) responses. Sera from term- and preterm-born infants were also collected and levels of IL-33 and type 2 cytokines were measured. Results: Neonatal hyperoxia induced asthma-like features including airway hyperresponsiveness, mucus hyperplasia, airway eosinophilia, and type 2 pulmonary inflammation. In addition, neonatal hyperoxia promoted allergic TH responses to house dust mite exposure. Elevated IL-33 levels and ILC2 responses were observed in the lungs most likely due to oxidative stress caused by neonatal hyperoxia. IL-33 receptor signaling and ILC2s were vital for the induction of asthma-like features following neonatal hyperoxia. Serum IL-33 levels correlated significantly with serum levels of IL-5 and IL-13 but not IL-4 in preterm infants. Conclusions: These data demonstrate that an axis involving IL-33 and ILC2s is important for the development of asthma-like features following neonatal hyperoxia and suggest therapeutic potential for targeting IL-33, ILC2s, and oxidative stress to prevent and/or treat asthma development related to prematurity.

KW - Asthma

KW - IL-33

KW - ILC2s

KW - Neonatal hyperoxia

KW - Oxidative stress

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