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Abstract：
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.
摘要：
尽管已经提出外源性氧化应激促进气道炎症的发病机制,以前使用常规抗氧化剂治疗哮喘的试验基本上无效，提示氧化应激在调节气道炎症及其关键介导淋巴细胞群中的复杂作用。第2组先天淋巴样细胞（ILC2s）在气道炎症的早期阶段响应于组织alarmin而增殖并诱导嗜酸性粒细胞增多。我们先前表明，IL-33诱导的内源性活性氧是ILC2功能最佳代谢激活所必需的，然而,外源性氧化应激在调节ILC2功能中的作用尚未被研究。这里,我们发现,注射ROS产生试剂诱导的外源性氧化应激减轻了IL-33引发的IL-33引起的ILC2反应和气道和肝脏炎症.ILC2s中的外源性氧化应激也损害了IL-33介导的这些细胞的积累，以及随后招募的嗜酸性粒细胞，过继转移到ILC2缺陷宿主后。机械上,ILC2s中的外源性氧化应激损害了增殖程序，同时保持效应分子在ILC2s中的表达水平。外源性氧化应激下的增殖受损导致ILC2s数量减少，和ILC2对IL-33刺激的反应总体降低。总的来说，这些数据表明，外源性氧化应激抑制ILC2s的增殖程序，减轻IL-33-触发的炎症，提示治疗性诱导氧化应激可能减轻ILC2介导的气道炎症，也可能在其他器官中。
