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Mice with type i interferon signaling deficiency are prone to epilepsy upon HSV-1 infection

Virologica Sinica 2024年第2期39卷 251-263页

作者： Wei Yang Chong-Yang Tang Dong-Ying Fan Yi-Song Wang Pei-Gang Wang Jing An Guo-Ming Luan Beijing Key Laboratory of Epilepsy Sanbo Brain HospitalCapital Medical UniversityBeijing100093China Beijing institute for Brain Disorders Capital Medical UniversityBeijing100093China Department of Neurosurgery Epilepsy CenterSanbo Brain HospitalCapital Medical UniversityBeijing100093China Department of Microbiology School of Basic Medical SciencesCapital Medical UniversityBeijing100069China Chinese institute for Brain Research Beijing102206China

Viral encephalitis continues to be a significant public health *** our previous study,we discovered a lower expression of antiviral factors,such as ifn-β,STiNG and iFi16,in the brain tissues of patients with Rasmussen's encephalitis(RE),a rare chronic neurological disorder often occurred in children,characterized by unihemispheric brain ***,a higher cumulative viral score of human herpes viruses(HHVs)was also found to have a significant positive correlation with the unihemispheric atrophy in *** i ifns(ifn-i)signaling is essential for innate anti-infection response by binding to ifn-α/βreceptor(ifnAR).in this study,we infected WT mice and ifnAR-deficient A6 mice with herpes simplex virus 1(HSV-1)via periocular injection to investigate the relationship between ifn-i signaling and HHVs-induced brain *** all mice exhibited typical viral encephalitis lesions in their brains,HSV-induced epilepsy was only observed in A6 *** gene expression matrix,functional enrichment analysis and protein-protein interaction network revealed four gene models that were positively related with HSV-induced ***,ten key genes with the highest scores were *** together,these findings indicate that intact ifn-i signaling can effectively limit HHVs induced neural symptoms and brain lesions,thereby confirming the positive correlation between ifn-i signaling repression and brain atrophy in RE and other HHVs encephalitis.

关键词： ifn-i signaling Human herpes viruses(HHVs) Rasmussen's encephalitis(RE)

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CD4^(+)T cells produce ifn-i to license cDC1s for induction of cytotoxic T-cell activity in human tumors

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Cellular & Molecular immunology 2024年第4期21卷 374-392页

作者： Xin Lei Daniël C.de Groot Marij J.P.Welters Tom de Wit Ellen Schrama Hans van Eenennaam Saskia J.Santegoets Timo Oosenbrug Annemarthe van der Veen Joris L.Vos Charlotte L.Zuur Noel F.C.C.de Miranda Heinz Jacobs Sjoerd H.van der Burg Jannie Borst Yanling Xiao Department of immunology Leiden University Medical CenterLeidenThe Netherlands Oncode institute Leiden University Medical CenterLeidenThe Netherlands Department of Tumor Biology and immunology The Netherlands Cancer InstituteAmsterdamThe Netherlands Department of Medical Oncology Oncode InstituteLeiden University Medical CenterLeidenThe Netherlands iMMiOS B.V. OssThe Netherlands Division of Medical Oncology The Netherlands Cancer InstituteAmsterdamThe Netherlands Department of Otorhinolaryngology Leiden University Medical Center LeidenThe Netherlands Department of Pathology Leiden University Medical CenterLeidenThe Netherlands

CD4^(+)T cells can"help"or"license" conventional type 1 dendritic cells(cDC1s)to induce CD8^(+)cytotoxic T lymphocyte(CTL)anticancer responses,as proven in mouse *** recently identified cDC1s with a transcriptomic imprint of CD4^(+)T-cell help,specifically in T-cell-infiltrated human cancers,and these cells were associated with a good prognosis and response to PD-1-targeting ***,we delineate the mechanism of cDC1 licensing by CD4^(+)T cells in *** CD4^(+)T cells produce ifnβvia the STiNG pathway,which promotes MHC-i antigen(cross-)presentation by cDC1s and thereby improves their ability to induce CTL anticancer *** cooperation with CD40 ligand(L),ifnβalso optimizes the costimulatory and other functions of cDC1s required for CTL response ***-i-producing CD4^(+)T cells are present in diverse T-cell-infiltrated cancers and likely deliver“help”signals to CTLs locally,according to their transcriptomic profile and colocalization with“helped/licensed”cDCs and tumor-reactive CD8^(+)T *** agreement with this scenario,the presence of ifn-i-producing CD4^(+)T cells in the TME is associated with overall survival and the response to PD-1 checkpoint blockade in cancer patients.

关键词： CD4^(+)T-cell help cDC1 licensing ifn-i signaling CD40 costimulation (cross-)presentation CTL priming Tumor control

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identification of risk factor for sepsis-related death by gene expression profiling analysis

Identification of risk factor for sepsis-related death by ge...

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第十二届全国免疫学学术大会

作者： Qi Yan Chen Xinxin Wu Na Cui Xueling Liu Zhonghui Department of immunology College of Basic Medical SciencesJilin University Department of Genetics College of Basic Medical SciencesJilin University

Sepsis is the common cause of death from systemic *** many efforts have been devoted for this life-threatening condition,it remains a lack of risk factor to evaluate the severity of *** we focused on the identificatio... 详细信息

关键词： Sepsis Gene expression profiling Survivor Risk factor ifn-i signaling

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