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Am. J. Respir. Crit. Care Med. · Sep 2017
Allergen-induced Increases in Sputum Levels of Group 2 Innate Lymphoid Cells in Asthmatic Subjects.
- Ruchong Chen, Steven G Smith, Brittany Salter, Amani El-Gammal, John Paul Oliveria, Caitlin Obminski, Rick Watson, Paul M O'Byrne, Gail M Gauvreau, and Roma Sehmi.
- 1 Asthma Research Group, Department of Medicine, Firestone Institute for Respiratory Health, St. Joseph's Healthcare and McMaster University, Hamilton, Ontario, Canada; and.
- Am. J. Respir. Crit. Care Med. 2017 Sep 15; 196 (6): 700-712.
RationaleGroup 2 innate lymphoid cells (ILC2), a major source of type 2 cytokines, initiate eosinophilic inflammatory responses in murine models of asthma.ObjectivesTo investigate the role of ILC2 in allergen-induced airway eosinophilic responses in subjects with atopy and asthma.MethodsUsing a diluent-controlled allergen challenge crossover study, where all subjects (n = 10) developed allergen-induced early and late responses, airway eosinophilia, and increased methacholine airway responsiveness, bone marrow, blood, and sputum samples were collected before and after inhalation challenge.Measurements And Main ResultsILC2 (lin-FcεRI-CD45+CD127+ST2+) and CD4+T lymphocytes were enumerated by flow cytometry, as well as intracellular IL-5 and IL-13 expression. Steroid sensitivity of ILC2 and CD4+ T cells was investigated in vitro. A significant increase in total, IL-5+, IL-13+, and CRTH2+ ILC2 was found in sputum, 24 hours after allergen, coincident with a significant decrease in blood ILC2. Total, IL-5+, and IL-13+, but not CRTH2+, CD4+ T cells significantly increased at 24 and 48 hours after allergen in sputum. In blood and bone marrow, only CD4+ cells demonstrated increased activation after allergen. Airway eosinophilia correlated with IL-5+ ILC2 at all time points and allergen-induced changes in IL-5+ CD4+ cells at 48 hours after allergen. Dexamethasone significantly attenuated IL-2- and IL-33-stimulated IL-5 and IL-13 production by both cell types.ConclusionsInnate and adaptive immune cells are increased in the airways associated with allergic asthmatic responses. Total and type 2 cytokine-positive ILC2 are increased only within the airways, whereas CD4+ T lymphocytes demonstrated local and systemic increases. Steroid sensitivity of both cells may explain effectiveness of this therapy in those with mild asthma.
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