Exogenous oxidative stress suppresses IL-33 -driven proliferation programming in group 2 innate lymphoid cells

•Exogenous oxidative stress dampened IL-33 –triggered ILC2 response and inflammation.•Exogenous oxidative stress in ILC2s compromised the recruitment of eosinophils.•Exogenous oxidative stress compromised the proliferation program in ILC2s. Although exogenous oxidative stress has been suggested to p...

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Published in:	International immunopharmacology 2021-06, Vol.95, p.107541-107541, Article 107541
Main Authors:	Zheng, Chaoyue, Lu, Zhen, Wu, Haisi, Cui, Lulu, Bi, Jiacheng, Wan, Xiaochun
Format:	Article
Language:	eng
Subjects:	Animals Antioxidants Asthma Cell Proliferation Cells, Cultured Eosinophilia Eosinophils Humans Inflammation Interleukin-33 - immunology Leukocytes (eosinophilic) Liver - immunology Lung Lung - immunology Lymphocytes Lymphocytes - immunology Lymphoid cells Metabolic activation Metabolic rate Mice Mice, Inbred C57BL Mice, Transgenic Organs Oxidation Oxidative Stress Pathogenesis Pulmonary inflammation Reactive oxygen species Reagents Respiratory tract Respiratory tract diseases Transcriptome Type 2 innate lymphoid cells
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Summary:	•Exogenous oxidative stress dampened IL-33 –triggered ILC2 response and inflammation.•Exogenous oxidative stress in ILC2s compromised the recruitment of eosinophils.•Exogenous oxidative stress compromised the proliferation program in ILC2s. Although exogenous oxidative stress has been suggested to promote the pathogenesis of airway inflammation, previous trials using conventional antioxidant therapy in asthma have been largely ineffective, suggesting the complex roles of oxidative stress in the regulation of airway inflammation and of its critical mediating lymphocyte populations. Group 2 innate lymphoid cells (ILC2s) proliferate and induce eosinophilia in response to tissue alarminsin the early phase of airway inflammation. We previously showed that IL-33 –induced endogenous reactive oxygen species is required for optimal metabolic activation of ILC2 functions, however, the role of exogenous oxidative stress in regulating ILC2 functions has not been investigated. Here, we found that exogenous oxidative stress induced by injection of ROS –generating reagent alleviated IL-33 –triggered ILC2 response and inflammation both in the airway and in the liver. Exogenous oxidative stress in ILC2s also compromised IL-33 –mediated accumulation of these cells, as well as subsequent recruitment of eosinophils, after adoptive transferring into ILC2 deficient hosts. Mechanistically, exogenous oxidative stress in ILC2s compromised the proliferation program, while preserving the expression levels of effector molecules in ILC2s. Impaired proliferation under exogenous oxidative stress led to reduced numbers of ILC2s, and an overall decrease in ILC2 response to IL-33 stimulation. Collectively, these data indicate that exogenous oxidative stress suppresses the proliferation program in ILC2s and alleviates IL-33 –triggered inflammation, suggesting that therapeutic induction of oxidative stress might alleviate ILC2 –mediated inflammation in the airway, and possibly also in other organs.
ISSN:	1567-5769 1878-1705