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mTOR regulates TLR-induced c-fos and Th1 responses to HBV and HCV vaccines

التفاصيل البيبلوغرافية
العنوان: mTOR regulates TLR-induced c-fos and Th1 responses to HBV and HCV vaccines
المؤلفون: Jianhua Xiao, Jing Mu, Dapeng Ma, Dapeng Li, Ke Lan, Chun Zhou, Qiang Deng, Xulin Huang, Lijian Hui, Hui Xiao, Min Du, Zhong Huang, Li He, Huimin Yan, Huanjing Shi, Sidong Xiong, Aiping Zang, Xiaoxia Li, Chuanping Yuan
المصدر: Virol Sin
بيانات النشر: Elsevier BV, 2015.
سنة النشر: 2015
مصطلحات موضوعية: MAPK/ERK pathway, Hepatitis B virus, Immunology, Priming (immunology), Hepacivirus, Biology, Mice, Virology, medicine, Animals, Cytotoxic T cell, Gene Regulatory Networks, Cells, Cultured, PI3K/AKT/mTOR pathway, B cell, Regulation of gene expression, Innate immune system, Macrophages, TOR Serine-Threonine Kinases, Toll-Like Receptors, Viral Vaccines, Dendritic Cells, Th1 Cells, Interleukin-12, Interleukin-10, Cell biology, CTL, medicine.anatomical_structure, Gene Expression Regulation, Molecular Medicine, Proto-Oncogene Proteins c-fos, Research Article
الوصف: Although IL-12 plays a critical role in priming Th1 and cytotoxic T lymphocyte (CTL) responses, Toll-like receptor (TLR) signaling only induces low amounts of IL-12 in dendritic cells and macrophages, implying the existence of stringent regulatory mechanisms. In this study, we sought to uncover the mechanisms underlying TLR-induced IL-12 expression and the Th1 response. By systemic screening, we identified a number of protein kinases involved in the regulation of TLRinduced IL-12 expression. In particular, PI3K, ERK, and mTOR play critical roles in the TLR-induced Th1 response by regulating IL-12 and IL-10 production in innate immune cells. Moreover, we identified c-fos as a key molecule that mediates mTOR-regulated IL-12 and IL-10 expression in TLR signaling. Mechanistically, mTOR plays a crucial role in c-fos expression, thereby modulating NFκB binding to promoters of IL-12 and IL-10. By controlling the expression of a special innate gene program, mTOR can specifically regulate the TLR-induced T cell response in vivo. Furthermore, blockade of mTOR by rapamycin efficiently boosted TLR-induced antigen-specific T and B cell responses to HBV and HCV vaccines. Taken together, these results reveal a novel mechanism through which mTOR regulates TLR-induced IL-12 and IL-10 production, contributing new insights for strategies to improve vaccine efficacy.
تدمد: 1995-820X
1674-0769
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::33e0eb13dc2568b0c6720461b2b74862
https://doi.org/10.1007/s12250-015-3606-3
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....33e0eb13dc2568b0c6720461b2b74862
قاعدة البيانات: OpenAIRE
الوصف
تدمد:1995820X
16740769