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| 1 | Increased Tim-3 expression alleviates liver injury by regulating macrophage activation in MCD-induced NASH mice显示文摘As an immune checkpoint,Tim-3 plays roles in the regulation of both adaptive and innate immune cells including macrophages and is greatly involved in chronic liver diseases.However,the precise roles of Tim-3 in nonalcoholic steatohepatitis(NASH)remain unstated.In the current study,we analyzed Tim-3 expression on different subpopulations of liver macrophages and further investigated the potential roles of Tim-3 on hepatic macrophages in methionine and choline-deficient diet(MCD)-induced NASH mice.The results of flow cytometry demonstrated the significantly increased expression of Tim-3 on all detected liver macrophage subsets in MCD mice,including F4/80^(+)CD11b^(+),F4/80^(+)CD68^(+),and F4/80^(+)CD169^(+)macrophages.Remarkably,Tim-3 knockout(KO)significantly accelerated MCD-induced liver steatosis,displaying higher serum ALT,larger hepatic vacuolation,more liver lipid deposition,and more severe liver fibrosis.Moreover,compared with wild-type C57BL/6 mice,Tim-3 KO MCD mice demonstrated an enhanced expression of NOX2,NLRP3,and caspase-1 p20 together with increased generation of IL-1βand IL-18 in livers.In vitro studies demonstrated that Tim-3 negatively regulated the production of reactive oxygen species(ROS)and related downstream pro-inflammatory cytokine secretion of IL-1βand IL-18 in macrophages.Exogenous administration of N-Acetyl-L-cysteine(NAC),a small molecular inhibitor of ROS,remarkably suppressed caspase-1 p20 expression and IL-1βand IL-18 production in livers of Tim-3 KO mice,thus significantly reducing the severity of steatohepatitis induced by MCD.In conclusion,Tim-3 is a promising protector in MCD-induced steatohepatitis by controlling ROS and the associated pro-inflammatory cytokine production in macrophages. | Xianhong Du Zhuanchang Wu Yong Xu Yuan Liu Wen Liu Tixiao Wang Chunyang Li Cuijuan Zhang Fan Yi Lifen Gao Xiaohong Liang Chunhong Ma | 2019 | Cellular & Molecular Immunology2019，16，11： | 9 |
| 2 | Hepatitis B virus evades immune recognition via RNA adenosine deaminase ADAR1-mediated viral RNA editing in hepatocytes显示文摘HBV is considered as a“stealth”virus that does not invoke interferon(IFN)responses;however,the mechanisms by which HBV bypasses innate immune recognition are poorly understood.In this study,we identified adenosine deaminases acting on RNA 1(ADAR1),which is a key factor in HBV evasion from IFN responses in hepatocytes.Mechanically,ADAR1 interacted with HBV RNAs and deaminated adenosine(A)to generate inosine(I),which disrupted host immune recognition and thus promoted HBV replication.Loss of ADAR1 or its deficient deaminase activity promoted IFN responses and inhibited HBV replication in hepatocytes,and blocking the IFN signaling pathways released the inhibition of HBV replication caused by ADAR1 deficiency.Notably,the HBV X protein(HBx)transcriptionally promoted ADAR1 expression to increase the threshold required to trigger intrinsic immune activation,which in turn enhanced HBV escape from immune recognition,leading to persistent infection.Supplementation with 8-azaadenosine,an ADAR1 inhibitor,efficiently enhanced liver immune activation to promote HBV clearance in vivo and in vitro.Taken together,our results delineate a molecular mechanism by which HBx promotes ADAR1-derived HBV immune escape and suggest a targeted therapeutic intervention for HBV infection. | Liyuan Wang Yang Sun Xiaojia Song Zehua Wang Yankun Zhang Ying Zhao Xueqi Peng Xiaodong Zhang Chunyang Li Chengjiang Gao Nailin Li Lifen Gao Xiaohong Liang Zhuanchang Wu Chunhong Ma | 2021 | Cellular & Molecular Immunology2021，18，8： | 2 |
| 3 | Tumor suppressor p53 functions as an essential antiviral molecule against Japanese encephalitis virus显示文摘Japanese encephalitis virus(JEV)is a mosquito-borne virus of the family Flaviviridae.It is the causative agent of Japanese encephalitis with approximately 50,000 infection cases and 10,000 fatal cases annually in Asia(Erlanger et al.,2009).Although liveattenuated JEV vaccine has been developed and used for human and pig vaccination,JE occurs epidemically or sporadically | Xufang Deng Jianchao Wei Zixue Shi Wenjun Yan Zhuanchang Wu Donghua Shao Beibei Li Ke Liu Xiaodu Wang Yafeng Qiu Zhiyong Ma | 2016 | Journal of Genetics and Genomics2016，43，12： | 1 |
| 4 | Palmitoylation of SARS-CoV-2 S protein is essential for viral infectivity显示文摘Dear Editor,Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is the causative agent of the unprecedented coronavirus disease 2019(COVID-19).SARS-CoV-2 entry into host cells is mediated by the viral transmembrane spike(S)glycoprotein that forms homotrimers protruding from the viral surface. | Zhuanchang Wu Zhaoying Zhang Xin Wang Jing Zhang Caiyue Ren Yuming Li Lifen Gao Xiaohong Liang Peihui Wang Chunhong Ma | 2021 | Signal Transduction and Targeted Therapy2021，6，7： | 1 |
| 5 | Peptide targeting the interaction of S protein cysteine-rich domain with Ezrin restricts pan-coronavirus infection显示文摘Dear Editor,To date,seven human coronaviruses(HCoVs)have been identified,among which the highly pathogenic severe acute respiratory syndrome-associated coronavirus(SARS-CoV),Middle East respiratory syndrome coronavirus(MERS-CoV),and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)have caused public health disasters worldwide. | Zhuanchang Wu Xiaobo Lei Xin Wang Zhaoying Zhang Yuming Li Lifen Gao Xiaohong Liang Peihui Wang Jianwei Wang Chunhong Ma | 2023 | Signal Transduction and Targeted Therapy2023，8，2： | 0 |
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