A Natural Killer T cell subset that protects against airway hyperreactivity

Publication date: Available online 29 May 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Ya-Ting Chuang, Krystle Leung, Ya-Jen Chang, Rosemarie H. DeKruyff, Paul B. Savag, Richard Cruse, Christophe Benoit, Dirk Elewaut, Nicole Baumgarth, Dale T. Umetsu
BackgroundInfection 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.ObjectiveWe characterized this specific NKT cell subpopulation that developed during influenza infection in neonatal mice and that suppressed the subsequent development of AHR.MethodsA cell surface marker was identified by comparing the mRNA expression profile of WT 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.ResultsWe showed that DN NKT cells with high CD38 expression produced IFN-γ, but not IL-17, IL-4 or IL-13, and inhibited the 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-CD38^hi NKT cell numbers.ConclusionThese results suggest that early/neonatal exposure to infection or antigenic 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 may protect against the development of allergic asthma and may be further explore as a protective measure for young children.

Graphical abstract

Teaser

A novel NKT cell subset expands in mice after influenza infection that prevents asthma. This mechanism, which explains the protective effects afforded by childhood environmental exposures, can be reproduced by treatments that activate NKT cells.


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