國家衛生研究院 NHRI:Item 3990099045/13221
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    题名: Environmental factor-mediated transgenerational inheritance of Igf2r hypomethylation and pulmonary allergic response via targeting dendritic cells
    作者: Suen, JL;Wu, TT;Li, YH;Lee, CL;Kuo, FC;Yan, PS;Wu, CF;Tran, M;Wang, CJ;Hung, CH;Wu, MT;Chan, MWY;Huang, SK
    贡献者: National Institute of Environmental Health Sciences
    摘要: The developmental origin of allergic diseases has been suggested, but the molecular basis remains enigmatic. Exposure to environmental factors, such as di-(2-ethylhexyl) phthalate (DEHP; a common plasticizer), is suggested to be associated with increased childhood allergic asthma, but the causal relationship and its underlying mechanism remain unknown. This study explored the transgenerational mechanism of DEHP on allergic asthma and dendritic cell (DC) homeostasis through epigenetic modification. In a murine model, ancestral exposure of C57BL/6 mice to low-dose DEHP led to trans-generational promoter hypomethylation of the insulin-like growth factor 2 receptor (Igf2r), concomitant with enhanced Igf2r expression and increased apoptosis prominently in CD8 alpha(+) DCs upon ligand stimulation, with consequent reduction in their IL-12 secretion and subsequent T cell-derived IFN-gamma, thereby promoting a default Th2-associated pulmonary allergic response. Increased apoptosis was also noted in circulating IGF2R(high) human DCs. Further, in human placenta, the methylation level at the orthologous IGF2R promoter region was shown to be inversely correlated with the level of maternal DEHP intake. These results support the importance of ancestral phthalate exposure in conferring the trans-generational risk of allergic phenotypes, featuring hypo-methylation of the IGF2R gene and dysregulated DC homeostasis.
    日期: 2020-12-23
    關聯: Frontiers in Immunology. 2020 Dec 23;11:Article number 603831.
    Link to: http://dx.doi.org/10.3389/fimmu.2020.603831
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1664-3224&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000605960000001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85099123263
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