A natural killer T-cell subset that protects against airway hyperreactivity

Ya Ting Chuang, Krystle Leung, Ya Jen Chang, Rosemarie H. DeKruyff, Paul B. Savage, Richard Cruse, Christophe Benoit, Dirk Elewaut, Nicole Baumgarth, Dale T. Umetsu

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Infection of suckling mice with influenza virus expands a CD4CD8 double-negative (DN) natural killer T (NKT) cell subpopulation that protects the mice as adults against allergen-induced airway hyperreactivity (AHR). However, this NKT cell subset has not been characterized, and the underlying mechanisms of protection remain unknown. Objective: We characterized this specific NKT cell subpopulation that developed during influenza infection in neonatal mice and that suppressed the subsequent development of AHR. Methods: A cell-surface marker was identified by comparing the mRNA expression profile of wild-type CD4+ NKT cells with that of suppressive Vα14 DN NKT cells. The marker-enriched NKT cell subset was then analyzed for its cytokine profile and its suppressive in vitro and in vivo abilities. Results: We showed that DN NKT cells with high CD38 expression produced IFN-γ, but not IL-17, IL-4, or IL-13, and inhibited development of AHR through contact-dependent suppression of helper CD4 T-cell proliferation. The NKT subset expanded in the lungs of neonatal mice after infection with influenza and also after treatment of neonatal mice with Nu–α-GalCer, which effectively increased DN CD38hi NKT cell numbers. Conclusion: These results suggest that early/neonatal exposure to infection or antigen challenge affects subsequent lung immunity by altering the cellular composition of cells in the lung and that some subsets of NKT cells suppress AHR. These results provide a possible mechanism by which prior infections can protect against the development of allergic asthma and might be further explored as a protective measure for young children.

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

Fingerprint

Natural Killer T-Cells
T-Lymphocyte Subsets
Infection
Lung
Human Influenza
Interleukin-13
Interleukin-17
Helper-Inducer T-Lymphocytes
Orthomyxoviridae
Cellular Immunity
Interleukin-4
Allergens
Asthma
Cell Count
Cell Proliferation
Cytokines
Antigens
Messenger RNA

Keywords

  • airway hyperreactivity
  • asthma
  • CD38
  • hygiene hypothesis
  • influenza
  • Natural killer T subset

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Chuang, Y. T., Leung, K., Chang, Y. J., DeKruyff, R. H., Savage, P. B., Cruse, R., ... Umetsu, D. T. (Accepted/In press). A natural killer T-cell subset that protects against airway hyperreactivity. Journal of Allergy and Clinical Immunology. https://doi.org/10.1016/j.jaci.2018.03.022

A natural killer T-cell subset that protects against airway hyperreactivity. / Chuang, Ya Ting; Leung, Krystle; Chang, Ya Jen; DeKruyff, Rosemarie H.; Savage, Paul B.; Cruse, Richard; Benoit, Christophe; Elewaut, Dirk; Baumgarth, Nicole; Umetsu, Dale T.

In: Journal of Allergy and Clinical Immunology, 01.01.2018.

Research output: Contribution to journalArticle

Chuang, YT, Leung, K, Chang, YJ, DeKruyff, RH, Savage, PB, Cruse, R, Benoit, C, Elewaut, D, Baumgarth, N & Umetsu, DT 2018, 'A natural killer T-cell subset that protects against airway hyperreactivity', Journal of Allergy and Clinical Immunology. https://doi.org/10.1016/j.jaci.2018.03.022
Chuang, Ya Ting ; Leung, Krystle ; Chang, Ya Jen ; DeKruyff, Rosemarie H. ; Savage, Paul B. ; Cruse, Richard ; Benoit, Christophe ; Elewaut, Dirk ; Baumgarth, Nicole ; Umetsu, Dale T. / A natural killer T-cell subset that protects against airway hyperreactivity. In: Journal of Allergy and Clinical Immunology. 2018.
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abstract = "Background: Infection of suckling mice with influenza virus expands a CD4−CD8− double-negative (DN) natural killer T (NKT) cell subpopulation that protects the mice as adults against allergen-induced airway hyperreactivity (AHR). However, this NKT cell subset has not been characterized, and the underlying mechanisms of protection remain unknown. Objective: We characterized this specific NKT cell subpopulation that developed during influenza infection in neonatal mice and that suppressed the subsequent development of AHR. Methods: A cell-surface marker was identified by comparing the mRNA expression profile of wild-type CD4+ NKT cells with that of suppressive Vα14 DN NKT cells. The marker-enriched NKT cell subset was then analyzed for its cytokine profile and its suppressive in vitro and in vivo abilities. Results: We showed that DN NKT cells with high CD38 expression produced IFN-γ, but not IL-17, IL-4, or IL-13, and inhibited development of AHR through contact-dependent suppression of helper CD4 T-cell proliferation. The NKT subset expanded in the lungs of neonatal mice after infection with influenza and also after treatment of neonatal mice with Nu–α-GalCer, which effectively increased DN CD38hi NKT cell numbers. Conclusion: These results suggest that early/neonatal exposure to infection or antigen challenge affects subsequent lung immunity by altering the cellular composition of cells in the lung and that some subsets of NKT cells suppress AHR. These results provide a possible mechanism by which prior infections can protect against the development of allergic asthma and might be further explored as a protective measure for young children.",
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AU - Savage, Paul B.

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AU - Benoit, Christophe

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AU - Umetsu, Dale T.

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