Chlorinated flame-retardant dechloranes are emerging substitutes for restricted flame retardants. Recent studies have demonstrated that they are accumulated in wildlife and detectable in humans; however, their effects on human health are poorly understood. Here, for the first time, we revealed that widely used chlorinated flame-retardant dechlorane 602 (Dec 602) exacerbated airway inflammation in two mouse models induced by house dust mite (HDM) or IL-33, respectively. Deteriorated airway inflammation by Dec 602 was associated with a higher production of type 2 cytokines including IL-4, IL-5, and IL-13, and IgE, accompanied by enhanced mRNA expression of proinflammatory cytokines such as TNF-alpha and IL-6. Mechanistically, we found that Dec 602 directly potentiated mouse and human group 2 innate lymphoid cells and, as such, promoted airway inflammation even in the absence of conventional T cells in Rag(-/-) mice. These findings provide novel immunological insights necessary for further studies of the health impact of emerging flame-retardant dechloranes including Dec 602.
基金:
Priority Research Program of the Shandong Academy of Sciences; Special Foundation of Taishan Scholars; Shandong Provincial Natural Science Foundation [ZR2016YL013, ZR2015YL005, 2017GSF19111]; National Natural Science Foundation of China (NSFC) [81600692, 81970759, 81803539]; Youth Science Funds of Shandong Academy of Sciences [2018QN003]; Six Talent Peaks Project in Jiangsu Province [2017-WSN-186]; Bellbery-Viertel Senior Medical Research Fellowship