Group 2 innate lymphoid cells promote airway hyperresponsiveness through production of VEGFA.
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ABSTRACT:
SUBMITTER: Shen X
PROVIDER: S-EPMC6019125 | biostudies-literature | 2018 May
REPOSITORIES: biostudies-literature
Publications
Group 2 innate lymphoid cells promote airway hyperresponsiveness through production of VEGFA.
Shen Xiaofei X Pasha Muhammad Asghar MA Hidde Kelsi K Khan Adil A Liang Mingwei M Guan Wenxian W Ding Yitao Y Haczku Angela A Yang Qi Q
The Journal of allergy and clinical immunology 20180131 5
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Project description:BackgroundGroup 2 innate lymphoid cells (ILC2s) are critical mediators of type 2 respiratory inflammation, releasing IL-5 and IL-13 and promoting the pulmonary eosinophilia associated with allergen provocation. Although ILC2s have been shown to promote eosinophil activities, the role of eosinophils in group 2 innate lymphoid cell (ILC2) responses is less well defined.ObjectiveWe sought to investigate the role of eosinophils in activation of ILC2s in models of allergic asthma and in vitro.MethodsInducible eosinophil-deficient mice were exposed to allergic respiratory inflammation models of asthma, such as ovalbumin or house dust mite challenge, or to innate models of type 2 airway inflammation, such as inhalation of IL-33. Eosinophil-specific IL-4/13-deficient mice were used to address the specific roles for eosinophil-derived cytokines. Direct cell interactions between ILC2s and eosinophils were assessed by in vitro culture experiments.ResultsTargeted depletion of eosinophils resulted in significant reductions of total and IL-5+ and IL-13+ lung ILC2s in all models of respiratory inflammation. This correlated with reductions in IL-13 levels and mucus in the airway. Eosinophil-derived IL-4/13 was necessary for both eosinophil and ILC2 accumulation in lung in allergen models. In vitro, eosinophils released soluble mediators that induced ILC2 proliferation and G protein-coupled receptor-dependent chemotaxis of ILC2s. Coculture of ILC2s and IL-33-activated eosinophils resulted in transcriptome changes in both ILC2s and eosinophils, suggesting potential novel reciprocal interactions.ConclusionThese studies demonstrate that eosinophils play a reciprocal role in ILC2 effector functions as part of both adaptive and innate type 2 pulmonary inflammatory events.
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