调节性T细胞研究组

 组长：周旭宇　博士、研究员

 研究组研究方向

调节性T细胞（Treg）的抑制机理及其免疫调控机制研究，探索选择性干预Treg细胞和其他效应性T细胞，进行肿瘤、感染性和自身免疫性疾病的治疗。

 研究组研究内容及意义

1.Treg细胞的抑制机理及其免疫调控机制研究 

Treg细胞对维持自身免疫稳态至关重要，但也是肿瘤抑制性微环境形成的重要原因，课题组致力于研究Treg细胞的抑制机理及其免疫调控机制，并探索通过改变Treg细胞数量活性等，对肿瘤和自身免疫性疾病进行干预。 

2.肿瘤TCR-T治疗研究 

利用课题组已经成熟建立的转基因小鼠筛选平台和TCR验证系统，基于高通量大数据，对肝癌等重要肿瘤TCR进行序列分析、鉴定和验证，以期找到行之有效的杀伤肿瘤细胞的TCR克隆，促进肿瘤TCR-T细胞治疗研究。 

 研究组长

课题组长：周旭宇 

电 话：010-64806075　 

电子邮件：zhouxy@im.ac.cn 

通讯地址：北京市朝阳区北辰西路1号院3号 

邮 编：100101 

 主要学习及工作经历

1989-1993 年 山东大学 学士

1993-1996 年 山东农业大学 硕士（师从温孚江教授）

1997-2001 年 大阪大学 博士（师从Toshiyuki Hamaoka教授）

2001-2003 年 大阪大学 交流学者/研究助理

2003-2009 年 美国加州大学旧金山分校（UCSF），博士后（师从Jeffery A. Bluestone教授）

2009-至今　 中国科学院微生物研究所 研究员、博士生导师

 研究团队

工作人员 

宋福行 副研究员 

张建华 助理研究员 

郭 洁 研究实习员 

在读研究生 

2014博：张雪洁 

2015博：谷千冲 

2016博：王 婷 

2017博：李丽萍 

2018博：曹 雪 

2016硕：张会玲 

2017硕：徐 威 

2018硕：柴 馨 

2019硕：张 秦 

已毕业学生 

2009博：胡探宇     

2010博：魏训东 

2010博：张忠美 

2011博：黄 满 

2011博：朱雪平 

2013硕：邹芒阁 

2015硕：赵修峰 

已离开工作人员 

张 伟 助理研究员 

郝淮杰 助理研究员 

郭基涛 博士后 

袁梦荷 博士后 

 代表性论文 　　  

1.  Zhang Z,Zhou X. Foxp3 Instability Helps tTregs Distinguish Self and Non-self.Front Immunol. 2019 Sep 24; 10: 2226. doi: 10.3389/fimmu.2019.02226. eCollection 2019.

2.  Xueping Zhu, Wei Zhang, Jie Guo, Xuejie Zhang, Liping Li, Ting Wang, Jinghua Yan, Fuping Zhang, Baidong Hou, Ning Gao,George F Gao*,Xuyu Zhou*. Noc4L mediated ribosome biogenesis controls activation of regulatory T cell and conventional T cell.Cell Reports. 2019, 27(4): 1205-1220

3.  Krung Phiwpan,Xuyu Zhou*. MicroRNAs in regulatory T cells.Cancer Letters, 2018, 423, 80-85.

4.  Xundong Wei, Jianhua Zhang, Qianchong Gu, Man Huang, Wei Zhang, Jie Guo,Xuyu Zhou*. Reciprocal Expression of IL-35 and IL-10 Defines Two Distinct Effector Treg Subsets that Are Required for Maintenance of Immune Tolerance.Cell Reports. 2017, 21(7), 1853-1869.

5.  Zhongmei Zhang, Wei Zhang, Jie Guo, Qianchong Gu, Xueping Zhu,Xuyu Zhou*. Activation and Functional Specialization of Regulatory T Cells Lead to the Generation of Foxp3 Instability.Journal of Immunology. 2017, 198(7): 2612-2625.

6. Decong Kong, Zhe Chen, Junping Wang, Qingyu Lv, Hua Jiang, Yuling Zheng, Maokai Xu,Xuyu Zhou*,Huaijie Hao*, Yongqiang Jiang*. Interaction of factor H-binding protein of Streptococcus suis with globotriaosylceramide promotes the development of meningitis.Virulence. 2017, 8(7): 1290-1302.

7. Man Huang, Wei Zhang, Jie Guo, Xundong Wei, Krung Phiwpan, Jianhua Zhang*,Xuyu Zhou*. Improved Transgenic Mouse Model for Studying HLA Class I Antigen Presentation.Scientific Reports. 2016, doi:10.1038/srep33612.

8. Tanyu Hu, Krung Phiwpan, Jitao Guo, Wei Zhang, Jie Guo, Zhongmei Zhang, Mangge Zou, Xuejie Zhang, Jianhua Zhang,Xuyu Zhou*. MicroRNA-142-3p Negatively Regulates Canonical Wnt Signaling Pathway.PLoS One, 2016, DOI:10.1371/journal.pone.0158432

9. Jitao Guo andXuyu Zhou*. Regulatory T cells turn pathogenic.Cellular & Molecular Immunology(2015), 1–8.

10.   Krung Phiwpan, Jie Guo, Wei Zhang, Tanyu Hu, Bhargavi M Boruah, Jianhua Zhang,Xuyu Zhou*. A novel transgenic mouse line for tracing microRNA-155-5p activity in vivo.PLoS One. 2015, 10(6):e0128198.

11. Jitao Guo, Jianhua Zhang, Xuejie Zhang, Zhongmei Zhang, Xundong Wei andXuyu Zhou*. Constitutive activation of MEK1 promotes Treg cell instability in vivo.Journal of Biological Chemistry. 2014, 289(51):35139-48.

12.  Peipei Liu, Di Liu, Xi Yang, Jing Gao, Yan Chen, Xue Xiao, Fei Liu1, Jing Zou, Jun Wu, Juncai Ma, Fangqing Zhao,Xuyu Zhou*, George F. Gao*, Baoli Zhu*. Characterization of human αβTCR repertoire and discovery of D-D fusion in TCR β chains.Protein & Cell. 2014, 5(8):603-15.

13. Lv Q, Hao H, Bi L, Zheng Y,Zhou X*, Jiang Y*. Suilysin remodels the cytoskeletons of human brain microvascular endothelial cells by activation RhoA and Rac1 GTPase.Protein & Cell. 2014, 5(4):261-4

14.  Hao H, Hui W, Liu P, Lv Q, Zeng X, Jiang H, Wang Y, Zheng X, Zheng Y, Li J*,Zhou X*, Jiang Y*. Effect of licochalcone A on growth and properties of Streptococcus suis.PLoS One. 2013, 8(7):e67728.

15.  Zhou X, Bailey-Bucktrout S, Jeker LT, Bluestone JA*. Plasticity of CD4(+) FoxP3(+) T cells.Curr Opin Immunol. 2009 Jun, 21(3):281-5. Review.

16. Zhou X, Bailey-Bucktrout SL, Jeker LT, Penaranda C, Martínez-Llordella M, Ashby M, Nakayama M, Rosenthal W, Bluestone JA*. Instability of the transcription factor Foxp3 leads to the generation of pathogenic memory T cells in vivo.Nat Immunol. 2009 Sep, 10(9):1000-7.

17. Zhou X, Jeker LT, Fife BT, Zhu S, Anderson MS, McManus MT, Bluestone JA*. Selective miRNA disruption in T reg cells leads to uncontrolled autoimmunity.J Exp Med. 2008 Sep 1, 205(9):1983-91.

18. Zhou, XY, Yashiro-Ohtani, Y, Toyo-oka, K, Park, CS, Tai, XG, Hamaoka, T, Fujiwara, H*. CD5 costimulation up-regulates the signaling to extracellular signal-regulated kinase activation in CD4(+)CD8(+) thymocytes and supports their differentiation to the CD4 lineage.The Journal of Immunology, 164(3): 1260-1268.

19. Zhou, XY, Yashiro-Ohtani, Y, Nakahira, M, Park, WR\, Abe, R, Hamaoka, T, Naramura, M, Gu, H, Fujiwara, H*. Molecular mechanisms underlying differential contribution of CD28 versus non-CD28 costimulatory molecules to IL-2 promoter activation.The Journal of Immunology, 168(8): 3847-3854.

20.  张雪洁，张建华，张伟，郭洁，周旭宇*，小鼠T-bet逆转录病毒载体的构建与功能验证，生物工程学报，2014，30（10），1586-1593

 研究中代表性图片

 1. 新型效应性Treg细胞亚群IL-35-Treg

Xundong Wei,et al.Cell Reports. 2017, 21(7), 1853-1869.

 Xueping Zhu,et al.Cell Reports.2019, 27(4): 1205-1220

申请专利

1.周旭宇，张建华，张伟，黄满；一种优化型HLA-I类转基因小鼠的构建方法；专利号：ZL 2015 1 0136784.5；授权日期：2019年7月12日

2.周旭宇，魏训东，徐威，张建华，黄满；HLA-A11限制性乙型肝炎病毒HBc141-151表位肽的T细胞受体及其应用；专利号：201911170818.7 (受理)

3.周旭宇，高福，赵欣，张会玲，璩骁，郭洁，张建华；埃博拉病毒感染细胞模型的制备与应用；专利号：201911147438.1 (受理)