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| 1 | Contribution of Toll-like receptors to the control of hepatitis B virus infection by initiating antiviral innate responses and promoting specific adaptive immune responses显示文摘适应免疫在肝炎 B 的控制起一个关键作用,这很好被接受病毒(HBV ) 感染。相反,天生的免疫的贡献仅仅在最近的年里收到了注意。像使用费的受体(TLR ) 察觉到联系病原体的分子模式并且激活抗病毒的机制,包括细胞内部的抗病毒的小径和抗病毒的受动器干扰素(IFN ) 和支持 inflammatory cytokines 的生产。从在 vitro 并且在 vivo 模型的试验性的结果证明了 TLR 调停细胞的发信号的小径和抗病毒的 cytokines 的生产的激活,导致 HBV 复制的抑制。然而, HBV 感染在主人房间和下游地表明小径的激活的封锁上与 TLR 表示的 downregulation 被联系。在主要 HBV 感染, TLR 可以减慢 HBV 感染,但是仅仅间接地作出贡献到病毒的清理。重要地, TLR 可以在 vivo 调制 HBV 特定的 T 房间和 B 房间回答,它为 HBV 感染的结束是必要的。因此, TLR 收缩筋正在答应候选人为长期的 HBV 感染的处理充当 immunomodulators。抗病毒的处理可以在长期的 HBV 感染恢复 TLR 表示和功能并且可以基于 TLR 激活增加治疗学的途径的功效。有抗病毒的治疗和 TLR 激活的联合治疗学的策略能便于 HBV 特定的有免疫力的回答的恢复并且从而,在长期地感染的 HBV 病人完成病毒的清理。 | Zhiyong Ma Ejuan Zhang Dongliang Yang Mengji Lu | 2015 | Cellular & Molecular Immunology2015，12，3： | 22 |
| 2 | Over-activation of TLR5 signaling by high-dose flagellin induces liver injury in mice显示文摘Flagellin 是涉及天生、适应的免疫的大量房间类型的有势力使活跃之物。因此,它是疫苗的一个好辅助候选人,并且它可能在癌症放射疗法和放射紧急情况的一个缓和者期间对主要尖锐放射症候群作为生物杀虫撒布剂工作。然而,积累证据含有在一些煽动性的疾病的出现的 flagellin 例如尖锐的肺发炎,心血管的倒塌和煽动性的肠疾病。这研究的目的是阐明 flagellin-TLR5 发信号激活是否仅仅或是否在肝的 pathophysiology 起一个作用某另外的 flagellin 活动也经由细菌的感染或在临床的应用期间贡献肝损害。Recombinant flagellin 蛋白质与或没有刺激 TLR5 活动被用来评估 flagellin-TLR5 在肝损害发信号在的角色野类型并且 TLR5 击倒老鼠。粗野损害和 hepatocellular 坏死的大区域在 100 或 200 µ 的 intraperitoneal 管理以后在肝织物 12 h 被观察;在一个剂量依赖者的 g flagellin (警察) 和在野类型的老鼠,然而并非在 TLR5 击倒老鼠的时间依赖者举止。flagellin 的 N 终端或 TLR5 绑定域的删除禁止了导致 flagellin 的煽动性的回答和随后的尖锐的肝函数反常和损坏。这些数据证实 flagellin 是肝损害的一个必要决定因素并且证明由高剂量的 flagellin 发信号的 TLR5 的在激活上在肝引起了尖锐煽动性的回答,嗜中性的累积和氧化应力,它贡献导致 flagellin 的肝损害的前进和严厉。 | Yang Xiao Fang Liu Jingyi Yang Maohua Zhong Ejuan Zhang Yaoming Li Dihan Zhou Yuan Cao Wei Li Jie Yu Yi Yang Huimin Yan | 2015 | Cellular & Molecular Immunology2015，12，6： | 9 |
| 3 | The IL-1R/TLR signaling pathway is essential for efficient CD8+ T-cell responses against hepatitis B virus in the hydrodynamic injection mouse model显示文摘The outcome of hepatitis B viral(HBV)infection is determined by the complex interactions between replicating HBV and the immune system.While the role of the adaptive immune system in the resolution of HBV infection has been studied extensively,the contribution of innate immune mechanisms remains to be defined.Here we examined the role of the interleukin-1 receptor/Toll-like receptor(IL-1R/TLR)signaling pathway in adaptive immune responses and viral clearance by exploring the HBV mouse model.Hydrodynamic injection with a replication-competent HBV genome was performed in wild-type mice(WT)and a panel of mouse strains lacking specific innate immunity component expression.We found higher levels of HBV protein production and replication in Tlr2^(−/−),Tlr23479^(−/−),3d/Tlr24^(−/−),Myd88/Trif^(−/−)and Irak4^(−/−)mice,which was associated with reduced HBV-specific CD8+T-cell responses in these mice.Importantly,HBV clearance was delayed for more than 2 weeks in 3d/Tlr24^(−/−),Myd88/Trif^(−/−)and Irak4^(−/−)mice compared to WT mice.HBV-specific CD8+T-cell responses were functionally impaired for producing the cytokines IFN-γ,TNF-αand IL-2 in TLR signaling-deficient mice compared to WT mice.In conclusion,the IL-1R/TLR signaling pathway might contribute to controlling HBV infection by augmenting HBV-specific CD8+T-cell responses. | Zhiyong Ma Jia Liu Weimin Wu Ejuan Zhang Xiaoyong Zhang Qian Li Gennadiy Zelinskyy Jan Buer Ulf Dittmer Carsten J Kirschning Mengji Lu | 2017 | Cellular & Molecular Immunology2017，14，12： | 6 |
| 4 | NLRC4 downregulates 的激活对 flagellin 的调停 TLR5 的抗体免疫者回答显示文摘细菌的 flagellin 是一个唯一的联系病原体的分子的模式(PAMP ) ,它能被表面认出局部性的像使用费的受体 5 (TLR5 ) 并且 cytosolic 像点头的受体(NLR ) 蛋白质 4 (NLRC4 ) 受体。由 flagellin 和产生有免疫力的回答戏表明小径的 TLR5 或 NLRC4 的激活在抗菌剂免疫的重要角色。然而,它仍然保持不清楚怎么 flagellin 的双活动激活 TLR5 或 NLRC4 发信号小径安排有免疫力的回答。在这研究,我们估计了缺乏能力对 flagellin 在适应有免疫力的回答上独自或在联合激活 TLR5 和 NLRC4 的 flagellin 和它的异种的效果。是不能的激活 NLRC4 的 Flagellin 比的导致了显著地更高的抗体回答野类型的 flagellin。当巨噬细胞在 vivo 被弄空时,增加的抗体反应能被消除。由 flagellin downregulated 的 NLRC4 的激活对 flagellin 的导致 flagellin 、调停 TLR5 的有免疫力的回答。 | Wei Li Jingyi Yang Ejuan Zhang Maohua Zhong Yang Xiao Jie Yu Dihan Zhou Yuan Cao Yi Yang Yaoming Li Huimin Yan | 2016 | Cellular & Molecular Immunology2016，13，4： | 5 |
| 5 | Calcium phosphate nanoparticles show an effective activation of the innate immune response in vitro and in vivo after functionalization with flagellin显示文摘For subunit vaccines,adjuvants play a key role in shaping the magnitude,persistence and form of targeted antigen-specific immune response.Flagellin is a potent immune activator by bridging innate inflammatory responses and adaptive immunity and an adjuvant candidate for clinical application.Calcium phosphate nanoparticles are efficient carriers for different biomolecules like DNA,RNA,peptides and proteins.Flagellin-functionalized calcium phosphate nanoparticles were prepared and their immunostimuiatory effect on the innate immune system,i.e.the cytokine production,was studied.They induced the production of the proinflammatory cytokines IL-8(Caco-2 cells) and IL-1β(bone marrow-derived macrophages;BMDM) in vitro and IL-6 in vivo after intraperitoneal injection in mice.The immunostimulation was more pronounced than with free flagellin. | Diana Kozlova Viktoriya Sokolova Maohua Zhong Ejuan Zhang Jingyi Yang Wei Li Yi Yang Jan Buer Astrid Maria Westendorf Matthias Epple Huimin Yan | 2014 | Virologica Sinica2014，29，1： | 3 |
| 6 | Longitudinal Characteristics of T Cell Responses in Asymptomatic SARS-CoV-2 Infection显示文摘Dear Editor,SARS-Co V-2 causes a spectrum of illness,ranging from an asymptomatic state to life-threatening multi-organ failure,and imposes a high socioeconomic burden on its sufferers and on society(Chen et al.2020;Pan et al.2020). | Jingyi Yang Ejuan Zhang Maohua Zhong Qingyu Yang Ke Hong Ting Shu Dihan Zhou Jie Xiang Jianbo Xia Xi Zhou Dingyu Zhang Chaolin Huang You Shang Huimin Yan | 2020 | Virologica Sinica2020，35，6： | 1 |
| 7 | Antigen replace- ment of domains D2 and D3 in flagellin promotes mueasal IgA pro- duetion and attenuates flagellin-indueed inflammatory response after intranasal immunization显示文摘 | Ymlg Jingyi Zhong Maohua Zhang Ejuan | 2013 | Human Vaccines and lmmm/othera- peutlees2013，9，5： | 1 |
| 8 | Broad phenotypic alterations and potential dysfunction of lymphocytes in individuals clinically recovered from COVID-19显示文摘Although millions of patients have clinically recovered from COVID-19,little is known about the immune status of lymphocytes in these individuals.In this study,the peripheral blood mononuclear cells of a clinically recovered(CR)cohort were comparatively analyzed with those of an age-and sex-matched healthy donor cohort.We found that CD8^(+)T cells in the CR cohort had higher numbers of effector T cells and effector memory T cells but lower Tc1(IFN-γ^(+)),Tc2(IL-4^(+)),and Tc17(IL-17A^(+))cell frequencies.The CD4^(+)T cells of the CR cohort were decreased in frequency,especially the central memory T cell subset.Moreover,CD4^(+)T cells in the CR cohort showed lower programmed cell death protein 1(PD-1)expression and had lower frequencies of Th1(IFN-γ^(+)),Th2(IL-4^(+)),Th17(IL-17A^(+)),and circulating follicular helper T(CXCR5^(+)PD-1^(+))cells.Accordingly,the proportion of isotype-switched memory B cells(IgM−CD20^(hi))among B cells in the CR cohort showed a significantly lower proportion,although the level of the activation marker CD71 was elevated.For CD3−HLA-DR−lymphocytes in the CR cohort,in addition to lower levels of IFN-γ,granzyme B and T-bet,the correlation between T-bet and IFN-γ was not observed.Additionally,by taking into account the number of days after discharge,all the phenotypes associated with reduced function did not show a tendency toward recovery within 4-11 weeks.The remarkable phenotypic alterations in lymphocytes in the CR cohort suggest that severe acute respiratory syndrome coronavirus 2 infection profoundly affects lymphocytes and potentially results in dysfunction even after clinical recovery. | Jingyi Yang Maohua Zhong Ejuan Zhang Ke Hong Qingyu Yang Dihan Zhou Jianbo Xia Yao-Qing Chen Mingbo Sun Bali Zhao Jie Xiang Ying Liu Yang Han Mengxin Xu Xi Zhou Chaolin Huang You Shang Huimin Yan | 2021 | Journal of Molecular Cell Biology2021，13，3： | 0 |
| 9 | Activation of the TLR signaling pathway in CD8+ T cells counteracts liver endothelial cell-induced T cell tolerance显示文摘The Toll-like receptor(TLR)signaling pathway,which is composed of a group of highly conserved molecules,plays a critical role in the recognition of pathogen-associated molecular patterns(PAMPs).Innate immunity activated through the TLR signaling pathway serves as a first defense against infectious diseases.1 However,the exact function of TLR signaling in viral infections remains to be elucidated. | Ejuan Zhang Hu Yan Qian Li Ulf Dittmer Huimin Yan Mengji Lu | 2019 | Cellular & Molecular Immunology2019，16，9： | 0 |
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