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The innate immune sensing of genomic integrity

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The innate immune sensing of genomic integrity

第十一届全国免疫学学术大会

作者： richard A flavell Yale University School of Medicine Department of Immunobiology

Genomic instability is a hallmark of cancer,and policing this is therefore essential to *** this and many other reasons,extensive DNA repair mechanisms are encoded in our *** of these require sensing of DNA damage as a prerequisite for *** exposure to ionizing radiation induces massive cell death and severe damage to tissues containing actively

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Toll-like receptors (TLRs) signaling suppresses the apoptosis of virus-infected cells

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Toll-like receptors (TLRs) signaling suppresses the apoptosi...

中国畜牧兽医学会畜牧兽医生物技术学分会暨中国免疫学会兽医免疫分会第八次学术研讨会

作者： Vincent Deubel Mustapha Si-Tahar Lena Alexopoulou richard flavell Institut Pasteur Shanghai Chinese Academy of Sciences

Toll-like receptors(TLRs) are a family of immune receptors that recognize molecular patterns associated with microbial pathogens,and induce antimicrobial immune *** of viruses produce double-stranded RNA(dsRNA) during their *** of dsRNA by TLR3 as well as a growing list of cytosolic sensors,such as dsRNA-activated protein kinase

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reatment of allergic inflammation and hyperresponsiveness by a simple compound, Bavachinin, isolated from Chinese herbs

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Cellular & Molecular Immunology 2013年第6期10卷 497-505页

作者： Xi Chen Ti Wen Jun Wei Zhenzhou Wu Puyue Wang Zhangyong Hong Liqing Zhao Bin Wang richard flavell Shumei Gao Min Wang Zhinan Yin Key Laboratory of Industrial Fermentation Microbiology (Tianjin University of Science and Technology) Ministry of Education College of Biotechnology Tianjin University of Science and Technology Tianjin China State Key Laboratory of Medicinal Chemical Biology College of Life Sciences Nankai University Tianjin China Department of Medical Oncology The First Hospital of China Medical University Shenyang China Key Laboratory of Medical Molecular Virology of MOE and MOH Fudan University Shanghai Medical College Shanghai China Department of Immunobiology Yale School of Medicine New Haven CT USA Tianjin University of Traditional Chinese Medicine Tianjin China

Asthmatic inflammation is mediated by a type 2 helper T cell （Th2） cytokine response, and blocking Th2 cytokine production is proven to have a potent therapeutic effect against asthmatic inflammation. Using IL-4-green fluorescent protein （GFP） reporter mice, we demonstrated that Bavachinin, a single compound isolated from a Chinese herb, significantly inhibited Th2 cytokine production, including IL-4, IL-5 and IL-13. Notably, this compound almost completely blocked inflammation in the ovalbumin （OVA）-sensitized animal asthma model. Furthermore, we demonstrated that this chemical selectively affects the level of GATA-3, most likely by affecting the stability of GATA-3 mRNA. Our results demonstrate, for the first time, the potential therapeutic value of this single compound derived from Chinese herbs.

关键词： asthma bavachinin IL-4

CFTR is a negative regulator ofγδT cell IFN-γproduction and antitumor immunity

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Cellular & Molecular Immunology 2021年第8期18卷 1934-1944页

作者： Yuanyuan Duan Guangqiang Li Miaomiao Xu Xiaofei Qi Mingxia Deng Xuejia Lin Zhiwei Lei Yi Hu Zhenghu Jia Quanli Yang Guangchao Cao Zonghua Liu Qiong Wen Zhenhua Li Jie Tang Wei Kevin Zhang Pingbo Huang Limin Zheng richard A.flavell Jianlei Hao Zhinan Yin Zhuhai Precision Medical Center Zhuhai People’s Hospital(Zhuhai Hospital Affiliated with Jinan University)Jinan UniversityZhuhai519000GuangdongChina The Biomedical Translational Research Institute Faculty of Medical ScienceJinan UniversityGuangzhou510632GuangdongChina Department of Physiology School of Basic Medical SciencesSouthern Medical UniversityGuangzhou510515GuangdongChina The First Affiliated Hospital Jinan UniversityGuangzhou510632China School of Pharmaceutical Sciences South-Central University for NationalitiesWuhan430074HubeiChina Division of Life Science Hong Kong University of Science and Technology(HKUST)Hong KongChina State Key Laboratory of Oncology in Southern China Collaborative Innovation Center for Cancer MedicineSun Yat-sen University Cancer CenterGuangzhou510060China Department of Immunobiology School of MedicineYale UniversityNew HavenCT06520USA

CFTR,a chloride channel and ion channel regulator studied mostly in epithelial cells,has been reported to participate in immune regulation and likely affect the risk of cancer ***,little is known about the effects of CFTR on the differentiation and function ofγδT *** this study,we observed that CFTR was functionally expressed on the cell surface ofγδT *** deletion and pharmacological inhibition of CFTR both increased IFN-γrelease by peripheralγδT cells and potentiated the cytolytic activity of these cells against tumor cells both in vitro and in ***,the molecular mechanisms underlying the regulation ofγδT cell IFN-γproduction by CFTR were either TCR dependent or related to Ca^(2+)*** was recruited to TCR immunological synapses and attenuated Lck-P38 MAPK-c-Jun *** addition,CFTR was found to modulate TCR-induced Ca^(2+)influx and membrane potential(Vm)-induced Ca^(2+)influx and subsequently regulate the calcineurin-NFATc1 signaling pathway inγδT ***,CFTR serves as a negative regulator of IFN-γproduction inγδT cells and the function of these cells in antitumor *** investigation suggests that modification of the CFTR activity ofγδT cells may be a potential immunotherapeutic strategy for cancer.

关键词： CFTR γδT cells TCR Membrane potential Antitumor immunity

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植物生物技术研究和发展——今后的十年

生物技术通报 1996年第4期12卷 1-4页

作者： richard B.flavell 朱遐

作为农业、园艺、食品、化学和制药工业更新基础的植物生物技术,日益受到重视。它为深化了解并改变植物生长和再产生新产物的基本过程和提高产力提供了方法。在今后的十年内,很可能将对植物基因组进行完全测序并对调控植物发育过程的大... 详细信息

作为农业、园艺、食品、化学和制药工业更新基础的植物生物技术,日益受到重视。它为深化了解并改变植物生长和再产生新产物的基本过程和提高产力提供了方法。在今后的十年内,很可能将对植物基因组进行完全测序并对调控植物发育过程的大量基因的功能进行分析。将分离农业上主要害虫、真菌、细菌和病毒的抗性基因并应用于农业。将开发含商业价值油类、蛋白和淀粉的种子,并将这种转基因作物应用于农业。由此将产生为消费者和工业提供新的选择形式的许多种植物;这将有利于与环境相适应的农业的发展。

关键词：植物生物技术研究和发展分子标记转基因作物马铃薯卷叶病毒抗性基因等位基因经济价值基因型与环境互作植物基因组

m6A mRNA methylation controls T cell homeostasis by targeting IL-7/STAT5/SOCS pathway

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m6A mRNA methylation controls T cell homeostasis by targetin...

第十二届全国免疫学学术大会

作者： Li Huabing Tong Jiyu Shu Zhu Yuval Kluger Matthew D.Simon Howard Y.Chang Zhinan Yin richard A.flavell Department of Immunobiology Yale University School of Medicine Shanghai Institute of Immunology Department of Microbiology and Immunology The First Affiliated Hospital Biomedical Translational Research Institute and Guangdong Province Key Laboratory of Molecular Immunology and Antibody Engineering Department of Pathology Yale University School of Medicine Department of Molecular Biophysics & Biochemistry Yale University Dynamic Regulomes Stanford University Howard Hughes Medical Institute

N6-methyladenosine(m6A)is the most common and abundant messenger RNA modification,modulated by‘writers’‘erasers’and‘readers’of this *** vitro data have shown that m6A influences all fundamental aspects of mRNA m... 详细信息

关键词： m6A methylation T cells STAT signaling Inflammation

Long time Cola beverages consumption aggravates the pathogenesis of EAE through modulating intestinal microbiota.

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Long time Cola beverages consumption aggravates the pathogen...

第十届全国免疫学学术大会

作者： Guangchao Cao Wanjun Huang Zonghua Liu Jiyu Tong Hao Cheng Yiming Wen Hengwen Yang Zhenzhou Wu Liqing Zhao richard A.flavell Zhinan Yin State Key Laboratory of Medicinal Chemical Biology College of Life Sicences Nankai University Guangdong Province Key Laboratory of Molecular Immunology and Antibody Engineering Biomedical Translational Innovative Entrepreneurial Team of Pearl River Talent ProgramBiomedical Translational Research Institute Jinan University Department of Immunology Yale School of Medicine

Epidemiological evidence has linked dietary changes,which may greatly disturb the homeostasis between immune system and microbiota,to the increasing incidence of autoimmune diseases in developed countries over recent *** Cola beverages had dramatically changed the dietary component all over the world in the past *** hypothesized that these commercial drinks may affect the pathogenesis of autoimmune diseases via modulating the composition of microbiota.

关键词： Cola beverages Microbiota EAE ATP

METTL3介导的m6A甲基修饰促进NK细胞抗肿瘤免疫

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METTL3介导的m6A甲基修饰促进NK细胞抗肿瘤免疫

第十四届全国免疫学学术大会

作者：宋浩宋佳茜程明郑美娟王田田莎 richard A flavell 朱书李华兵丁琛魏海明孙汭彭慧田志刚中国科学技术大学免疫学研究所安徽医科大学第一附属医院复旦大学附属中山医院耶鲁大学医学院上海交通大学医学院

NK细胞在抗肿瘤免疫应答中发挥着至关重要的作用,但肿瘤微环境中,NK细胞功能是否受到表观转录后调控仍不可知。在本项研究中,我们发现肿瘤微环境抑制NK细胞上mA编码器METTL3表达水平,而METTL3表达水平与NK细胞效应功能呈正相关。METTL3... 详细信息

NK细胞在抗肿瘤免疫应答中发挥着至关重要的作用,但肿瘤微环境中,NK细胞功能是否受到表观转录后调控仍不可知。在本项研究中,我们发现肿瘤微环境抑制NK细胞上mA编码器METTL3表达水平,而METTL3表达水平与NK细胞效应功能呈正相关。METTL3特异性缺陷导致稳态下NK细胞比例和数量降低,并且阻碍NK细胞在肿瘤微环境中的浸润及其效应功能,因此加速肿瘤生长,使得小鼠生存期显著缩短。进一步分析发现,PTPN11能够同时被mA修饰及METTL3结合,并且METTL3缺陷促使SHP-2(PTPN11)蛋白水平显著下调。SHP-2活动被抑制后,NK细胞中AKT及MAPK磷酸化水平下降,从而无法完全响应微环境中IL-15信号。总而言之,我们的研究首次证实mA甲基转移酶METTL3是NK细胞稳态维持和抗肿瘤免疫的坚实后盾。

关键词： NK 肿瘤 m6A METTL3 SHP-2 IL-15

Nature:研究鉴定出蛋白Nlrp9b抵抗轮状病毒感染机制

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现代生物医学进展 2017年第27期17卷 I0002-I0002页

作者： Shu Zhu, Zheng Wei, Noah W. Palm, Yi Yang, Hua Yu, Hua-Bing Li, Geng Wang, Xuqiu Lei, Marcel R. de Zoete, Jun Zhao, Yunjiang Zheng, Haiwei Chen, Liang Shan, richard A. flavell Siyuan Ding, Ningguo Feng, Harry B. Greenberg Siyuan Ding, Harry B. Greenberg Penghua Wang, Yujiao Zhao Wen Pan, Jun Lu Jun Zhao, Yuval Kluger Kellie A. Jurado, Clara Abraham, Erol Fikrig Erol Fikrig, richard A. flavell Department of Immunobiology Yale University School of Medicine New Haven Connecticut 06520 USA Department of Medicine and Department of Microbiology & Immunology Stanford University School of Medicine Stanford California 94305 USA Palo Alto Veterans Institute of Research VA Palo Alto Health Care System Palo Alto California 94304 USA Department of Microbiology and Immunology New York Medical College Valhalla New York 10595 USA Department of Genetics Yale University School of Medicine New Haven Connecticut 06520 USA Department of Pathology Yale University School of Medicine New Haven Connecticut 06520 USA Department of Internal Medicine Yale University School of Medicine New Haven Connecticut 06520 USA Howard Hughes Medical Institute Chevy Chase Maryland 20815 USA

轮状病毒（rotavirus）是婴儿和儿童罹患肠胃炎和腹泻的一种最为常见的原因，每年导致全世界大约21．5万人死亡。它是高度传染性的和潜在致命性的。这种病毒特异性地感染宿主小肠中的肠上皮细胞，并且已进化出抵抗干扰素和NF-KB信号的... 详细信息

轮状病毒（rotavirus）是婴儿和儿童罹患肠胃炎和腹泻的一种最为常见的原因，每年导致全世界大约21．5万人死亡。它是高度传染性的和潜在致命性的。这种病毒特异性地感染宿主小肠中的肠上皮细胞，并且已进化出抵抗干扰素和NF-KB信号的策略来躲避免疫系统，这就提出一个问题：其他的宿主因子是否参与肠道粘膜中的抗病毒反应。不过，针对体内（特别是通过NLR炎性体）检测和限制肠道病毒的机制，人们知之甚少。

关键词：感染机制轮状病毒蛋白鉴定肠上皮细胞 NF-KB 免疫系统肠道粘膜