TLR、CLR和RLR等天然免疫受体，既可以识别微生物携带的“模式分子”，启动免疫反应、实施宿主防御，也可以识别坏死细胞分泌的“损伤分子”，参与损伤修复、维持机体稳态。感受到病菌入侵或组织损伤后，TLR、CLR、RLR和cGAS/STING等“模式识别受体”通过复杂的信号分子网络，诱导上千种基因表达，参与炎症反应、免疫调节和组织重建等多种生理过程。但是当这些模式识别信号缺陷或失调时，则会导致慢性感染、炎症和肿瘤等疾病。

 

我们实验室主要研究方向是阐明模式识别受体信号的转导与调节机制，特别是天然免疫信号在DC细胞中介导T细胞亚群分化，调节免疫应答和免疫耐受的分子机制。最近我们通过一系列筛选发现了在TLR、CLR、RLR和cGAS/STING等天然免疫信号通路中分别起正、负调节作用的一些新分子。结合病人资源和动物模型，揭示了这些分子在天然免疫细胞（特别是树突细胞和巨噬细胞）和上皮细胞中调节细胞因子和干扰素表达，影响细胞代谢和细胞死亡的信号转导和表观遗传学机制。接下来我们将重点研究“模式识别受体”如何区分病原体、共生菌和癌变细胞，以启动合适的T细胞免疫反应的分子和细胞学机制，为研发抵御病菌感染、防治炎症和肿瘤的新策略提供理论依据。

   

071005-微生物学
071009-细胞生物学
083100-生物医学工程

探究TLR介导的天然免疫在抗感染中的作用以及新型佐剂的研发
TLR信号调节免疫反应的分子和细胞学机理
针对自身免疫性疾病和肿瘤的新型药物研发

1994-09--1997-07   中国科学院上海植物生理研究所   分子遗传学博士
1991-09--1994-07   武汉大学生命科学学院   微生物与免疫学硕士
1987-09--1991-07   武汉大学生命科学学院   微生物与免疫学学士

-- 研究生

-- 博士

病毒学
高级免疫学与病毒学系列讲座
天然免疫学
生物学进展论坛

   

（1） 中科院优秀博士论文指导教师, 研究所（学校）, 2017
（2） 最佳青年科学家奖, 特等奖, 其他, 2006

   

[1] Hu, Yanxiang, Wen, Jing, Zhang, Bei, Xiao, Hui. Precision control of mTORC1 is crucial for the maintenance and IL-13 responsiveness of alveolar macrophages. INTERNATIONAL IMMUNOPHARMACOLOGY[J]. 2021, 95: http://dx.doi.org/10.1016/j.intimp.2021.107552.
[2] Chen, Xia, Wang, Li, Cao, Limin, Li, Tiantian, Li, Zhihong, Sun, Yumeng, Ding, Jinqiu, Zhou, Chun, Xie, Yadong, Yue, Nan, Nan, Jing, Jia, XinMing, Peng, Chao, Li, Huabin, Yang, Jinbo, Xiao, Hui. Regulation of Anion Channel LRRC8 Volume-Regulated Anion Channels in Transport of 2 ' 3 '-Cyclic GMP-AMP and Cisplatin under Steady State and Inflammation. JOURNAL OF IMMUNOLOGY[J]. 2021, 206(9): 2061-2074, http://dx.doi.org/10.4049/jimmunol.2000989.
[3] 肖晖. TSC1 Suppresses Macrophage Necroptosis for the Control of Infection by Fungal Pathogen Candida albicans. Immunohorizons.. 2021, [4] Zhou, Chun, Chen, Xia, PlanellsCases, Rosa, Chu, Jiachen, Wang, Li, Cao, Limin, Li, Zhihong, LopezCayuqueo, Karen, I, Xie, Yadong, Ye, Shiwei, Wang, Xiang, Ullrich, Florian, Ma, Shixin, Fang, Yiyuan, Zhang, Xiaoming, Qian, Zhikang, Liang, Xiaozheng, Cai, ShiQing, Jiang, Zhengfan, Zhou, Dongming, Leng, Qibin, Xiao, Tsan S, Lan, Ke, Yang, Jinbo, Li, Huabin, Peng, Chao, Qiu, Zhaozhu, Jentsch, Thomas J, Xiao, Hui. Transfer of cGAMP into Bystander Cells via LRRC8 Volume-Regulated Anion Channels Augments STING-Mediated Interferon Responses and Anti-viral Immunity. IMMUNITY[J]. 2020, 52(5): 767-U305, http://dx.doi.org/10.1016/j.immuni.2020.03.016.
[5] Xie, Yadong, Zhao, Yifan, Shi, Lei, Li, Wei, Chen, Kun, Li, Min, Chen, Xia, Zhang, Haiwei, Li, Tiantian, MatsuzawaIshimoto, Yu, Yao, Xiaomin, Shao, Dianhui, Ke, Zunfu, Li, Jian, Chen, Yan, Zhang, Xiaoming, Cui, Jun, Cui, Shuzhong, Leng, Qibin, Cadwell, Ken, Li, Xiaoxia, Wei, Hong, Zhang, Haibing, Li, Huabin, Xiao, Hui. Gut epithelial TSC1/mTOR controls RIPK3-dependent necroptosis in intestinal inflammation and cancer. JOURNAL OF CLINICAL INVESTIGATION[J]. 2020, 130(4): 2111-2128, https://www.webofscience.com/wos/woscc/full-record/WOS:000530101000051.
[6] Wenjuan Wang, Zihou Deng, Hongyu Wu, Qun Zhao, Tiantian Li, Wencheng Zhu, Xiongjun Wang, Longhai Tang, Chengshu Wang, ShuZhong Cui, Hui Xiao, Jiangye Chen. A small secreted protein triggers a TLR2/4-dependent inflammatory response during invasive Candida albicans infection. NATURE COMMUNICATIONS[J]. 2019, 10(1): https://doaj.org/article/ac084d58804b4e069be3d084f85f3794.
[7] Lei Shi, Xia Chen, Aiping Zang, Tiantian Li, Yanxiang Hu, Shixin Ma, Mengdie L, Huiyong Yin, Haikun Wang, Xiaoming Zhang, Bei Zhang, Qibin Leng, Jinbo Yang, Hui Xiao. TSC1/mTOR-controlled metabolic-epigenetic cross talk underpins DC control of CD8+ T-cell homeostasis.. PLoS Biology[J]. 2019, 17(8): https://doaj.org/article/478d9bfaed80460896a86dbde0bc88a4.
[8] Zhang, Wenqian, Zhang, Huihui, Liu, Shujun, Xia, Fucan, Kang, Zijian, Zhang, Yan, Liu, Yaoyang, Xiao, Hui, Chen, Lei, Huang, Chuanxin, Shen, Nan, Xu, Huji, Li, Fubin. Excessive CD11c(+)Tbet(+) B cells promote aberrant T-FH differentiation and affinity-based germinal center selection in lupus. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA[J]. 2019, 116(37): 18550-18560, [9] Liu, Lulu, Wan, Xiaoling, Zhou, Peipei, Zhou, Xiaoyuan, Zhang, Wei, Hui, Xinhui, Yuan, Xiujie, Ding, Xiaodan, Zhu, Ruihong, Meng, Guangxun, Xiao, Hui, Ma, Feng, Huang, He, Song, Xianmin, Zhou, Bin, Xiong, Sidong, Zhang, Yan. The chromatin remodeling subunit Baf200 promotes normal hematopoiesis and inhibits leukemogenesis. JOURNAL OF HEMATOLOGY & ONCOLOGY[J]. 2018, 11(1): https://doaj.org/article/d7d99fa0a3434e59b227a1e2bcb032c4.
[10] Peipei Zhou, Xiaodan Ding, Xiaoling Wan, Lulu Liu, Xiujie Yuan, Wei Zhang, Xinhui Hui, Guangxun Meng, Hui Xiao, Bin Li, Jin Zhong, Fajian Hou, Lihwen Deng, Yan Zhang. MLL5 suppresses antiviral innate immune response by facilitating STUB1-mediated RIG-I degradation. NATURE COMMUNICATIONS[J]. 2018, 9(1): http://202.127.25.143/handle/331003/3439.
[11] Zhang, WuChang, Du, LinJuan, Zheng, XiaoJun, Chen, XiaoQing, Shi, Chaoji, Chen, BoYan, Sun, XueNan, Li, Chao, Zhang, YuYao, Liu, Yan, Xiao, Hui, Leng, Qibin, Jiang, Xinquan, Zhang, Zhiyuan, Sun, Shuyang, Duan, ShengZhong. Elevated sodium chloride drives type I interferon signaling in macrophages and increases antiviral resistance. JOURNAL OF BIOLOGICAL CHEMISTRY[J]. 2018, 293(3): 1030-1039, http://dx.doi.org/10.1074/jbc.M117.805093.
[12] Jianrong Wang, Nanhai He, Na Zhang, Dexian Quan, Shuo Zhang, Caroline Zhang, Ruth T Yu, Annette R Atkins, Ruihong Zhu, Chunhui Yang, Ying Cui, Christopher Liddle, Michael Downes, Hui Xiao, Ye Zheng, Johan Auwerx, Ronald M Evans, Qibin Leng. NCoR1 restrains thymic negative selection by repressing Bim expression to spare thymocytes undergoing positive selection. NATURE COMMUNICATIONS[J]. 2017, 8(1): https://doaj.org/article/44d61d03248845d2aefd7d87c420a9d8.
[13] Ma, Shixin, Wan, Xiaoling, Deng, Zihou, Shi, Lei, Hao, Congfang, Zhou, Zhenyuan, Zhou, Chun, Fang, Yiyuan, Liu, Jinghua, Yang, Jing, Chen, Xia, Li, Tiantian, Zang, Aiping, Yin, Shigang, Li, Bin, Plumas, Joel, Chaperot, Laurence, Zhang, Xiaoming, Xu, Guoliang, Jiang, Lubin, Shen, Nan, Xiong, Sidong, Gao, Xiaoming, Zhang, Yan, Xiao, Hui. Epigenetic regulator CXXC5 recruits DNA demethylase Tet2 to regulate TLR7/9-elicited IFN response in pDCs. JOURNAL OF EXPERIMENTAL MEDICINE[J]. 2017, 214(5): 1471-1491, https://www.webofscience.com/wos/woscc/full-record/WOS:000400379300019.
[14] 刘莹, 周纯, 刘晶华, 陈霞, 张文举, 肖晖. Wip1正调控TLR4信号介导I型干扰素的表达. 安徽农业大学学报[J]. 2017, 44(5): 844-851, http://lib.cqvip.com/Qikan/Article/Detail?id=673740422.
[15] Xingxing Zhu, Dongyan Shi, Xiaoqian Li, Weijuan Gong, Fengjiao Wu, Xuejiang Guo, Hui Xiao, Lixin Liu, Hong Zhou. TLR signalling affects sperm mitochondrial function and motility via phosphatidylinositol 3-kinase and glycogen synthase kinase-3α. Cellular Signalling. 2016, 28(3): 148-156, http://dx.doi.org/10.1016/j.cellsig.2015.12.002.
[16] Gong, Qi, Hu, Zhimin, Zhang, Feifei, Cui, Aoyuan, Chen, Xin, Jiang, Haoyang, Gao, Jing, Chen, Xuqing, Han, Yamei, Liang, Qingning, Ye, Dewei, Shi, Lei, Chin, Y Eugene, Wang, Yu, Xiao, Hui, Guo, Feifan, Liu, Yong, Zang, Mengwei, Xu, Aimin, Li, Yu. Fibroblast Growth Factor 21 Improves Hepatic Insulin Sensitivity by Inhibiting Mammalian Target of Rapamycin Complex 1 in Mice. HEPATOLOGY[J]. 2016, 64(2): 425-438, http://www.corc.org.cn/handle/1471x/2374568.
[17] Javed Numan, Xue Guang, Lu Ailing, Xing Yue, Iwakura Yoichiro, Xiao Hui, Lecoeur Herv, Spth Gerald F, Meng Guangxun. Cross reactivity of S. aureus to murine cytokine assays: A source of discrepancy. Cytokine[J]. 2016, [18] 肖晖. 逆转录病毒感染小鼠原代巨噬细胞方法研究. 安徽农业大学学报. 2016, [19] Deng, Zihou, Ma, Shixin, Zhou, Hao, Zang, Aiping, Fang, Yiyuan, Li, Tiantian, Shi, Huanjing, Liu, Mei, Du, Min, Taylor, Patricia R, Zhu, Helen He, Chen, Jiangye, Meng, Guangxun, Li, Fubin, Chen, Changbin, Zhang, Yan, Jia, XinMing, Lin, Xin, Zhang, Xiaoming, Pearlman, Eric, Li, Xiaoxia, Feng, GenSheng, Xiao, Hui. Tyrosine phosphatase SHP-2 mediates C-type lectin receptor-induced activation of the kinase Syk and anti-fungal T(H)17 responses. NATURE IMMUNOLOGY[J]. 2015, 16(6): 642-+, https://www.webofscience.com/wos/woscc/full-record/WOS:000354751900017.
[20] James, Sharmy J, Jiao, Huipeng, Teh, HongYing, Takahashi, Hirotaka, Png, Chin Wen, Phoon, Meng Chee, Suzuki, Youichi, Sawasaki, Tatsuy, Xiao, Hui, Chow, Vincent T K, Yamamoto, Naoki, Reynolds, Joseph M, Flavell, Richard A, Dong, Chen, Zhang, Yongliang. MAPK Phosphatase 5 Expression Induced by Influenza and Other RNA Virus Infection Negatively Regulates IRF3 Activation and Type I Interferon Response. CELL REPORTS[J]. 2015, 10(10): 1722-1734, http://dx.doi.org/10.1016/j.celrep.2015.02.030.
[21] Sharmy J James, Yu Xiang, Jinghua Liu, Ke Lan, Yadong Xie, Jin Zhong, Min Du, Xia Chen, Bing Sun, Chuanping Yuan, Mingzhou Chen, Hui Xiao, Yongliang Zhang. Casein Kinase II Controls TBK1/IRF3 Activation in IFN Response against Viral Infection. American Association of Immunologists. 2015, http://oa.las.ac.cn/oainone/service/browseall/read1?ptype=JA&workid=JA201902028358473ZK.
[22] 何丽, 熊思东, 肖晖. 骨髓来源巨噬细胞中有效地敲除floxed基因的新方案. 安徽农业大学学报[J]. 2015, 42(6): 898-903, [23] He, Li, Zang, Aiping, Du, Min, Ma, Dapeng, Yuan, Chuanping, Zhou, Chun, Mu, Jing, Shi, Huanjing, Li, Dapeng, Huang, Xulin, Deng, Qiang, Xiao, Jianhua, Yan, Huimin, Hui, Lijian, Lan, Ke, Xiong, Sidong, Li, Xiaoxia, Huang, Zhong, Xiao, Hui. mTOR regulates TLR-induced c-fos and Th1 responses to HBV and HCV vaccines. VIROLOGICA SINICA[J]. 2015, 30(3): 174-189, http://lib.cqvip.com/Qikan/Article/Detail?id=90666888504849534851484851.
[24] 肖晖. Non-Classical MHC I-E negatively regulates macrophage activation and Th17 cells in NOD mice. scientific reports. 2015, [25] Zhao, Qinglan, Liang, Deguang, Sun, Rui, Jia, Baosen, Xia, Tian, Xiao, Hui, Lan, Ke. Kaposi's Sarcoma-Associated Herpesvirus-Encoded Replication and Transcription Activator Impairs Innate Immunity via Ubiquitin-Mediated Degradation of Myeloid Differentiation Factor 88. JOURNAL OF VIROLOGY[J]. 2015, 89(1): 415-427, https://www.webofscience.com/wos/woscc/full-record/WOS:000347176100035.
[26] Wang, Chenhui, Wu, Ling, Bulek, Katarzyna, Martin, Bradley N, Zepp, Jarod A, Kang, Zizhen, Liu, Caini, Herjan, Tomasz, Misra, Saurav, Carman, Julie A, Gao, Ji, Dongre, Ashok, Han, Shujie, Bunting, Kevin D, Ko, Jennifer S, Xiao, Hui, Kuchroo, Vijay K, Ouyang, Wenjun, Li, Xiaoxia. The psoriasis-associated D10N variant of the adaptor Act1 with impaired regulation by the molecular chaperone hsp90. NATURE IMMUNOLOGY[J]. 2013, 14(1): 72-81, https://www.webofscience.com/wos/woscc/full-record/WOS:000312433800012.
[27] Cui, Wei, Xiao, Nengming, Xiao, Hui, Zhou, Hao, Yu, Minjia, Gu, Jun, Li, Xiaoxia. beta-TrCP-Mediated IRAK1 Degradation Releases TAK1-TRAF6 from the Membrane to the Cytosol for TAK1-Dependent NF-kappa B Activation. MOLECULAR AND CELLULAR BIOLOGY[J]. 2012, 32(19): 3990-4000, https://www.webofscience.com/wos/woscc/full-record/WOS:000308748100016.
[28] Kim, Tae Whan, Yu, Minjia, Zhou, Hao, Cui, Wei, Wang, Jianan, DiCorleto, Paul, Fox, Paul, Xiao, Hui, Li, Xiaoxia. Pellino 2 Is critical for Toll-like Receptor/Interleukin-1 Receptor (TLR/IL-1R)-mediated Post-transcriptional Control. JOURNAL OF BIOLOGICAL CHEMISTRY[J]. 2012, 287(30): 25686-25695, http://dx.doi.org/10.1074/jbc.M112.352625.
[29] Gulen, Muhammet F, Bulek, Katarzyna, Xiao, Hui, Yu, Minjia, Gao, Ji, Sun, Lillian, Beurel, Eleonore, KaidanovichBeilin, Oksana, Fox, Paul L, DiCorleto, Paul E, Wang, Jianan, Qin, Jun, Wald, David N, Woodgett, James R, Jope, Richard S, Carman, Julie, Dongre, Ashok, Li, Xiaoxia. Inactivation of the Enzyme GSK3 alpha by the Kinase IKKi Promotes AKT-mTOR Signaling Pathway that Mediates Interleukin-1-Induced Th17 Cell Maintenance. IMMUNITY[J]. 2012, 37(5): 800-812, https://www.webofscience.com/wos/woscc/full-record/WOS:000311460000008.
[30] Chan, Ernest R, Hester, James, Kalady, Matthew, Xiao, Hui, Li, Xiaoxia, Serre, David. A novel method for determining microflora composition using dynamic phylogenetic analysis of 16S ribosomal RNA deep sequencing data. GENOMICS[J]. 2011, 98(4): 253-259, http://dx.doi.org/10.1016/j.ygeno.2011.04.002.
[31] Yin, Weiguo, Wan, Youzhong, Kim, Tae Whan, Yao, Peng, Xiao, Hui, Zhou, Hao, Xiao, Jianhua, Fox, Paul, Li, Xiaoxia. The Kinase Activity of Interleukin-1 Receptor-Associated Kinase 2 Is Essential for Lipopolysaccharide-Mediated Cytokine and Chemokine mRNA Stability and Translation. JOURNAL OF INTERFERON AND CYTOKINE RESEARCH[J]. 2011, 31(5): 415-422, https://www.webofscience.com/wos/woscc/full-record/WOS:000290256000002.
[32] Gulen, Muhammet F, Kang, Zizhen, Bulek, Katarzyna, Youzhong, Wan, Kim, Tae Whan, Chen, Yi, Altuntas, Cengiz Z, BakJensen, Kristian Sass, McGeachy, Mandy J, Do, JeongSu, Xiao, Hui, Delgoffe, Greg M, Min, Booki, Powell, Jonathan D, Tuohy, Vincent K, Cua, Daniel J, Li, Xiaoxia. The Receptor SIGIRR Suppresses Th17 Cell Proliferation via Inhibition of the Interleukin-1 Receptor Pathway and mTOR Kinase Activation. IMMUNITY[J]. 2010, 32(1): 54-66, http://dx.doi.org/10.1016/j.immuni.2009.12.003.
[33] Xiao, Hui, Yin, Weiguo, Khan, Mohammed A, Gulen, Muhammet F, Zhou, Hang, Sham, Ho Pan, Jacobson, Kevan, Vallance, Bruce A, Li, Xiaoxia. Loss of Single Immunoglobulin Interlukin-1 Receptor-Related Molecule Leads to Enhanced Colonic Polyposis in Apc(min) Mice. GASTROENTEROLOGY[J]. 2010, 139(2): 574-585, http://dx.doi.org/10.1053/j.gastro.2010.04.043.
[34] 肖晖. IRAK2 is critical for LPS-mediated post-transcriptional control.. Journal of Biological Chemistry. 2009, [35] 肖晖. Pellino 3b negatively regulates IL-1-induced TAK1-dependent NF?B activation.. 2008, [36] 肖晖. The kinase activity of IRAK4 is required for TLR-IL-1R-induced TAK1-dependent NFB activation. J Biol Chem. 2008, [37] Von Bernuth, H, Picard, C, Jin, Z, Pankla, R, Xiao, H, Ku, C L, Chrabieh, M, Ben Mustapha, I, Gandhil, P, Camcioglu, Y, Vasconcelos, J, Sirvent, N, Guedes, M, Vitor, A B, HerreroMata, M J, Arostegui, J, I, de Liria, RodrigoGonzalez C, Alsina, L, RuizOrtiz, E, Juan, M, Fortuny, C, Yaguee, J, Anton, J, Pascal, M, Chang, H H, Janniere, L, Rose, Y, Garty, B Z, Chapel, H, Issekutz, A, Marodi, L. Pyogenic bacterial infections in humans with MyD88 deficiency. CLINICAL AND EXPERIMENTAL IMMUNOLOGYnull. 2008, 154: 213-213, https://www.webofscience.com/wos/woscc/full-record/WOS:000262727500411.
[38] 肖晖. Interleukin-1 (IL-1)-induced TAK1-dependent Versus MEKK3-dependent NFB activation pathways bifurcate at IRAK modification. J Biol Chem. 2007, [39] 肖晖. The Toll-Interleukin-1 receptor member SIGIRR regulates colonic epithelia homeostasis, inflammation and tumorigenesis. Immunity. 2007, [40] Jinzhong Qin, Jianhong Yao, Grace Cui, Hui Xiao, Tae Whan Kim, Jerzy Fraczek, Paul Wightman, Shintaro Sato, Shizuo Akira, Anne Puel, JeanLaurent Casanova, Bing Su, Xiaoxia Li. TLR8-mediated NF-κB and JNK Activation Are TAK1-independent and MEKK3-dependent. Journal of Biological Chemistry. 2006, 281(30): 21013-21021, http://dx.doi.org/10.1074/jbc.M512908200.
[41] Xiao, H, Chung, J, Kao, HY, Yang, YC. Tip60 is a co-repressor for STAT3. JOURNAL OF BIOLOGICAL CHEMISTRY[J]. 2003, 278(13): 11197-11204, https://www.webofscience.com/wos/woscc/full-record/WOS:000181855400045.
[42] 肖晖. Specificity of IL-2 receptor gamma chain superfamily cytokines is mediated by insulin receptor substrate-dependent pathway. J Biol Chem. 2002, [43] 肖晖. The Binding site and model of transcription activator SyrM to nodD3 promoter region. Science in China. 1998, [44] 肖晖. NifL, an antagonistic regulator of NifA, directly interacts with transcription activator NifA and NtrC. Science in China. 1998, [45] Kim Tae Whan, Staschke Kirk, Bulek Katarzyna, Yao Jianhong, Peters Kristi, Oh Keun-Hee, Vandenburg Yvonne, Xiao Hui, Qian Wen, Hamilton Tom, Min Booki, Sen Ganes, Gilmour Raymond, Li Xiaoxia. A critical role for IRAK4 kinase activity in Toll-like receptor–mediated innate immunity. The Journal of Experimental Medicine. 204(5): 1025-1036, https://www.webofscience.com/wos/woscc/full-record/WOS:000246467600008.

（1） toll样受体信号通路，Signaling by Toll-Like Receptors，Taylor and Francis Group, LLC，2008-07，第1作者
（2） 近代微生物学进展，progresses in morden microbiology，武汉大学出版社，1994-07，第1作者

已指导学生

刘晶华  02  63228  

邓子厚  01  19178  

现指导学生

谢亚栋  01  19178  

周纯  01  19178  

王青青  02  63228  

何丽  01  19178  

赵亦帆   02  19178