Influenza infection in suckling mice expands an NKT cell subset that protects against airway hyperreactivity

Ya Jen Chang, Hye Young Kim, Lee A. Albacker, Hyun Hee Lee, Nicole Baumgarth, Shizuo Akira, Paul B. Savage, Shin Endo, Takashi Yamamura, Janneke Maaskant, Naoki Kitano, Abel Singh, Apoorva Bhatt, Gurdyal S. Besra, Peter Van Den Elzen, Ben Appelmelk, Richard W. Franck, Guangwu Chen, Rosemarie H. DeKruyff, Michio ShimamuraPetr Illarionov, Dale T. Umetsu

Research output: Contribution to journalArticle

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Abstract

Infection with influenza A virus represents a major public health threat worldwide, particularly in patients with asthma. However, immunity induced by influenza A virus may have beneficial effects, particularly in young children, that might protect against the later development of asthma, as suggested by the hygiene hypothesis. Herein, we show that infection of suckling mice with influenza A virus protected the mice as adults against allergen-induced airway hyperreactivity (AHR), a cardinal feature of asthma. The protective effect was associated with the preferential expansion of CD4-CD8-, but not CD4+, NKT cells and required T-bet and TLR7. Adoptive transfer of this cell population into allergen-sensitized adult mice suppressed the development of allergen-induced AHR, an effect associated with expansion of the allergen-specific forkhead box p3+ (Foxp3+) Treg cell population. Influenza-induced protection was mimicked by treating suckling mice with a glycolipid derived from Helicobacter pylori (a bacterium associated with protection against asthma) that activated NKT cells in a CD1d-restricted fashion. These findings suggest what we believe to be a novel pathway that can regulate AHR, and a new therapeutic strategy (treatment with glycolipid activators of this NKT cell population) for asthma.

Original languageEnglish (US)
Pages (from-to)57-69
Number of pages13
JournalJournal of Clinical Investigation
Volume121
Issue number1
DOIs
StatePublished - Jan 4 2011

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Natural Killer T-Cells
Human Influenza
Asthma
Allergens
Influenza A virus
Infection
Glycolipids
Hygiene Hypothesis
Population
Adoptive Transfer
Regulatory T-Lymphocytes
Helicobacter pylori
Immunity
Public Health
Bacteria
Therapeutics

ASJC Scopus subject areas

  • Medicine(all)

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Influenza infection in suckling mice expands an NKT cell subset that protects against airway hyperreactivity. / Chang, Ya Jen; Kim, Hye Young; Albacker, Lee A.; Lee, Hyun Hee; Baumgarth, Nicole; Akira, Shizuo; Savage, Paul B.; Endo, Shin; Yamamura, Takashi; Maaskant, Janneke; Kitano, Naoki; Singh, Abel; Bhatt, Apoorva; Besra, Gurdyal S.; Van Den Elzen, Peter; Appelmelk, Ben; Franck, Richard W.; Chen, Guangwu; DeKruyff, Rosemarie H.; Shimamura, Michio; Illarionov, Petr; Umetsu, Dale T.

In: Journal of Clinical Investigation, Vol. 121, No. 1, 04.01.2011, p. 57-69.

Research output: Contribution to journalArticle

Chang, YJ, Kim, HY, Albacker, LA, Lee, HH, Baumgarth, N, Akira, S, Savage, PB, Endo, S, Yamamura, T, Maaskant, J, Kitano, N, Singh, A, Bhatt, A, Besra, GS, Van Den Elzen, P, Appelmelk, B, Franck, RW, Chen, G, DeKruyff, RH, Shimamura, M, Illarionov, P & Umetsu, DT 2011, 'Influenza infection in suckling mice expands an NKT cell subset that protects against airway hyperreactivity', Journal of Clinical Investigation, vol. 121, no. 1, pp. 57-69. https://doi.org/10.1172/JCI44845
Chang, Ya Jen ; Kim, Hye Young ; Albacker, Lee A. ; Lee, Hyun Hee ; Baumgarth, Nicole ; Akira, Shizuo ; Savage, Paul B. ; Endo, Shin ; Yamamura, Takashi ; Maaskant, Janneke ; Kitano, Naoki ; Singh, Abel ; Bhatt, Apoorva ; Besra, Gurdyal S. ; Van Den Elzen, Peter ; Appelmelk, Ben ; Franck, Richard W. ; Chen, Guangwu ; DeKruyff, Rosemarie H. ; Shimamura, Michio ; Illarionov, Petr ; Umetsu, Dale T. / Influenza infection in suckling mice expands an NKT cell subset that protects against airway hyperreactivity. In: Journal of Clinical Investigation. 2011 ; Vol. 121, No. 1. pp. 57-69.
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