Humoral immune regulation, particularly in the following areas:

1. Molecular mechanisms governing cell-cell interactions in Germinal center reaction;

2. How cell fate determination in Germinal centers is controlled by the qualitative and quantitative parameters of cell-cell interactions;

3. Molecular mechanisms regulating the spatial-temporal organization of B cell follicles and germinal centers;

4. How the three layers of regulations described above is coordinated to ensured efficient humoral immune response but at the same time prevent autoimmunity;

5. Molecular mechanisms regulating differentiation and maintenance of memory B cells and long-lived plasma cells;

6. Regulation of immune response by the central nervous system.

We are also interested in studying:

7. Sexual dimorphism in immune response;

8. Differentiation of tissue resident CD8 T cells;

9. Microglia biology.

ORCID: 0000-0001-5475-3989

Bibliography: (# corresponding author; * co-first authors)

1. 1. Bo Liu, Yihan Lin, Jiacong Yan, Jiacheng Yao, Dan Liu, Weiwei Ma, Jianbin Wang, Wanli Liu, Chengshuo Wang, Luo Zhang, and Hai Qi^#. Affinity-coupled CCL22 promotes positive selection in germinal centres. Nature, 202 (DOI: 10.1038/s41586-021-03239-2)
2. 2. Hai Qi. New twists in humoral immune regulation by SLAM family receptors. Journal of Experimental Medicine, 218 (3): e20202300, 2021. (Commentary)
3. 3. Xingya Ni^*, Yifeng Wang^*, Pei Wang, Coco Chu, Heping Xu, Jinzhi Hu, Jiahui Sun, and Hai Qi^#. Death associated protein kinase 2 suppresses T-B interactions and GC formation. Molecular Immunology, 2020. (DOI: 10.1016/j.molimm.2020.10.018)
4. 4. Xu Zhang^*, Bo Lei^*, Yuan Yuan^*, Li Zhang^*, Lu Hu, Sen Jin, Bilin Kang, Xuebin Liao, Wenzhi Sun, Fuqiang Xu, Yi Zhong^#, Ji Hu^# and Hai Qi^#. Brain control of humoral immune responses amenable to behavioral modulation. Nature, 581:204-208, 2020.
5. 5. Ruozhu Zhao, Xin Chen, Weiwei Ma, Jinyu Zhang, Jie Guo, Xiu Zhong, Jiacheng Yao, Jiahui Sun, Julian Rubinfien, Xuyu Zhou, Jianbin Wang and Hai Qi^#. A GPR174-CCL21 module imparts sexual dimorphism to humoral immunity. Nature, 577:416-420, 2020.
6. 6. Zurong Wan, Yihan Lin, Yongshan Zhao, and Hai Qi^#. T_FH cells in bystander and cognate interactions with B cells. Immunological Reviews, 288:28-36, 2019.
7. 7. Zurong Wan, Xingxing Shao, Xingyu Ji, Lihui Dong, Jiacheng Wei, Zhuqing Xiong, Wanli Liu and Hai Qi^#. Transmembrane domain-mediated Lck association underlies bystander and costimulatory ICOS signaling. Cellular & Molecular Immunology, 2018. (DOI: 10.1038/s41423-018-0183-z).
8. 8. Xiangjun Chen, Xiaolin Sun, Wei Yang, Bing Yang, Xiaozhen Zhao, Shuting Chen, Lili He, Hui Chen, Changmei Yang, Le Xiao, Zai Chang, Jianping Guo, Jing He, Fuping Zhang, Fang Zheng, Zhibin Hu, Zhiyong Yang, Jizhong Lou, Wenjie Zheng, Hai Qi, Chenqi Xu, Hong Zhang, Hongying Shan, Xujie Zhou, Qingwen Wang, Yi Shi, Luhua Lai, Zhanguo Li^#, and Wanli Liu^#. An autoimmune disease variant of IgG1 modulates B-cell activation and differentiation. Science, 362:700-705, 201
9. 9. Jingwen Shi, Shiyue Hou, Qian Fang, Xin Liu, Xiaolong Liu, and Hai Qi^#. PD-1 controls follicular T helper cell positioning and function. Immunity, 49:264-274, 2018.
10. 10. Jing Wang, Sichen Liu, Baidong Hou, Meixiang Yang, Zhongjun Dong, Hai Qi, Wanli Liu. PTEN-regulated AID transcription in germinal center B cells is essential for the class-switch recombination and IgG antibody responses. Frontiers in Immunology, 9:371, 2018.
11. 11. Juan Feng, Xin Liu, Xingya Ni and Hai Qi^#. External signals regulate germinal center fate-determining transcription factors in the A20 lymphoma cell line. Molecular Immunology, 93:79-86, 2018.
12. 12. Hai Qi. Nervous crosstalk to make antibodies. Nature, 547:288-290, 2017 (Commentary; July 12, 2017 AOP, doi:10.1038/nature23097).
13. 13. Chenguang Xu, Hengyi Xie, Xingdong Guo, Haipeng Gong, Lei Liu, Hai Qi, Chenqi Xu, Wanli Liu. A PIP2-derived amplification loop fuels the sustained initiation of B cell activation. Science Immunology, 2:eaan0787, 2017.
14. 14. Yifeng Wang^*, Jingwen Shi^*, Jiacong Yan^*, Zhengtao Xiao, Xiaoxiao Hou, Peiwen Lu, Shiyue Hou, Tianyang Mao, Wanli Liu, Yuanwu Ma, Lianfeng Zhang, Xuerui Yang and Hai Qi^#. Germinal center development of memory B cells driven by Interleukin-9-producing follicular T-helper cells. Nature Immunology, 18:921-930, 2017 (June 26, 2017 Epub ahead of print, doi:10.1038/ni.3788).
15. 15. Peiwen Lu^*, Changming Shih^*, and Hai Qi^#. Ephrin B1–mediated repulsion and signaling control germinal center T cell territoriality and function. Science, 356:eaai9264, 2017. (April 13, 2017 Epub ahead of print, doi:10.1126/science.aai9264).
16. 16. Changming Shih and Hai Qi^#. Intravital microscopy of T-B cell interactions in germinal centers. Methods in Molecular Biology, 1623:73-85, 2017
17. 17. Hu Yan^*, Longyan Wu^*, Changming Shih, Shiyue Hou, Jingwen Shi, Tianyang Mao, Wenbin Chen, Bhavani Melvin, Robert J. Rigby, Yingjia Chen, Haochen Jiang, Roland H. Friedel, Carola G. Vinuesa, and Hai Qi^#. Plexin B2 and Semaphorin 4C guide T-cell recruitment and function in the germinal center. Cell Reports, 19:995-1007, 20
18. 18. Jiacong Yan, Bo Liu, Yan Shi, Hai Qi^#. Class II MHC-independent suppressive adhesion of dendritic cells by regulatory T cells in vivo. Journal of Experimental Medicine, 214:319, 2017.
19. 19. Jiahuan Chen, Anutosh Ganguly, Ashley Mucsi, Junchen Meng, Jiacong Yan, Zongde Zhang, Pascal Detampel, Fay Munro, Mei Wu, Melanie Stenner, Wencheng Zheng, Paul Kubes, Matthias Amrein, Hai Qi, Aswin Hari, Tie Xia, Yan Shi. Strong adhesion by regulatory T cells induces dendritic cell cytoskeletal polarization and contact-dependent lethargy. Journal of Experimental Medicine, 214:327, 2017.
20. 20. Hai Qi^#. T follicular helper cells in space-time. Nature Reviews Immunology, 16:612-625, 2016.
21. 21. Ran He^*, Shiyue Hou^*, Cheng Liu^*, Anli Zhang, Qiang Bai, Miao Han, Yu Yang, Gang Wei, Ting Shen, Xinxin Yang, Lifan Xu, Xiangyu Chen, Yaxing Hao, Chuhong Zhu, Juanjuan Ou, Houjie Liang, Ting Ni, Xiaoyan Zhang, Xinyuan Zhou, Jianqing Xu^#, Hai Qi^#, Yuzhang Wu^# and Lilin Ye^#. Follicular CXCR5-expressing CD8 T cells curtail chronic viral infection. Nature, 537:412-428, (2016).
22. 22. Peng Wang, Chang-ming Shih, Hai Qi^#, Yue-heng Lan^#. A stochastic model of the germinal center integrating local antigen competition, individualistic T-B interactions and BCR signaling. Journal of Immunology, 197:1169-1182, 2016 (July 15, doi:10.4049/jimmunol.1600411).
23. 23. Shan Tang, Zhengpeng Wan, Yiren Gao, Ji-Shen Zheng, Jing Wang, Yan-Yan Si, Xin Chen, Hai Qi, Lei Liu, Wanli Liu. Total chemical synthesis of photoactivatable proteins for light-controlled manipulation of antigen–antibody interactions. Chemical Science (Jan 2016, doi:10.1039/C5SC03404C).
24. 24. Xiangjun Chen, Weiling Pan, Yinqiang Sui, Hua Li, Xiaoshan Shi, Xingdong Guo, Hai Qi, Chenqi Xu, and Wanli Liu. Acidic phospholipids govern the enhanced activation of IgG-B cell receptor. Nature Communications 6:8552, 2015 (Oct 6, doi: 10.1038/ncomms9552).
25. 25. Xin Chen^*#, Weiwei Ma^*, Tingxin Zhang, Longyan Wu, and Hai Qi^#. Phenotypic Tfh development promoted by CXCR5-controlled re-localization and IL-6 from radiation-resistant cells. Protein & Cell 6:825-832, 2015 (Sept 24, 2015 Epub ahead of print, doi:10.​1007/​s13238-015-0210-0).
26. 26. Weiwei Ma^*#, Ruozhu Zhao^*, Runqing Yang, Bo Liu, Xin Chen, Longyan Wu, and Hai Qi^#. Nuclear receptors of the NR4A family are not required for the development and function of follicular T helper cells. International Immunopharmacology 28:841-845, 2015 (April 18, 2015 Epub ahead of print, doi:10.1016/j.intimp.2015.04.012).
27. 27. Xin Chen^*, Shan Tang^*, Ji-Shen Zheng^*, Ruozhu Zhao, Zhi-Peng Wang, Wen Shao, Hao-Nan Chang, Jing-Yuan Cheng, Hui Zhao, Lei Liu^#, and Hai Qi^#. Chemical synthesis of a two-photon-activatable chemokine and photon-guided lymphocyte migration in vivo. Nature Communications 6:7220, 2015 (May 26, doi: 10.1038/ncomms8220).
28. 28. Dan Liu^*, Heping Xu^*, Changming Shih, Zurong Wan, Xiaopeng Ma, Weiwei Ma, Dan Luo, and Hai Qi^#. T-B-cell entanglement and ICOSL-driven feed-forward regulation of germinal centre reaction. Nature, 517:214-218, 2015 (Oct 15, 2014 Epub ahead of print, doi:10.1038/nature13803).
29. 29. Coco Chu, Yifeng Wang, Xu Zhang, Xinya Ni, Junxia Cao, Wan Xu, Zhongjun Dong, Pengfei Yuan, Wensheng Wei, Yuanwu Ma, Lianfeng Zhang, Longyan Wu, and Hai Qi^#. SAP-regulated T cell-APC adhesion and ligation-dependent and -independent Ly108-CD3z interactions. Journal of Immunology, 193:3860-3871, 2014 (Sep 12, Epub ahead of print, doi:10.4049/jimmunol.1401660)

30. 30. Hai Qi^#, Xin Chen, Coco Chu, Dan Liu, Weiwei Ma, Yifeng Wang, Longyan Wu, Hu Yan, and Jiacong Yan. Tfh cell differentiation and their function in promoting B-cell responses. Advances in Experimental Medicine and Biology, 841:153-180, 2014

31. 31. Hai Qi^#, Wolfgang Kastenmuller^# and Ronald N Germain^#. Spatio-temporal basis of innate and adaptive immunity in secondary lymphoid tissue. Annual Review of Cell and Developmental Biology, 30:141-167, 2014 (Aug 8, Epub ahead of print, doi: 10.1146/annurev-cellbio-100913-013254)
32. 32. Hai Qi^#, Dan Liu, Weiwei Ma, Yifeng Wang, Hu Yan. Bcl-6 controlled T_FH polarization and memory: the known unknowns. Current Opinion in Immunology, 28:34-41, 2014
33. 33. Junjiao Yang, Yuan Zhang, Pengfei Yuan, Yuexin Zhou, Changzu Cai, Qingpeng Ren, Dingqiao Wen, Coco Chu, Hai Qi, and Wensheng Wei. Complete decoding of TAL effectors for DNA recognition. Cell Research, 24:628-631, 2014
34. 34. Xindong Liu, Xin Chen, Bo Zhong, Yaoqi Alan Wang, Xiaohu Wang, Fuliang Chu, RozaNurieva, Xiaowei Yan, Ping Chen, Laurens van der Flier, Hiroko Nakatsukasa, SattvaNeelapu, Wanjun Chen, Hans Clevers, Qiang Tian, Hai Qi, Lai Wei, and Chen Dong. Transcription factor Achaete-Scute homologue 2 initiates T follicular helper cell development. Nature, 507:513-518, 2014
35. 35. Longyan Wu, Peiwen Lu, Weiwei Ma, Coco Chu, Heping Xu, and Hai Qi^#. Identification of a new isoform of the murine Sh2d1a gene and its functional implications. Science China Life Sciences 57: 1–7, 2014.
36. 36. Hai Qi^#, Xin Chen, CoCo Chu, Peiwen Lu, Heping Xu, and Jiacong Yan. Follicular T-helper cells: controlled localization and cellular interactions. Immunology & Cell Biology, 92:28-33, 2014.
37. 37. Seung Goo Kang*, Wen-Hsien Liu*, Peiwen Lu*, Hyun Yong Jin, Hyung W Lim, Jovan Shepherd, Daniel Fremgen, Eric Verdin, Michael B A Oldstone, Hai Qi, John R Teijaro, and Changchun Xiao. MiR-17~92 family microRNAs are critical regulators of T Follicular helper cell differentiation. Nature Immunology 14:849-57, 2013. (* co-first authors)
38. 38. Heping Xu, Xuanying Li, Dan Liu, Jianfu Li, Xu Zhang, Xin Chen, Shiyue Hou, Lixia Peng, Chenguang Xu, Wanli Liu, Lianfeng Zhang, and Hai Qi^#. Follicular T-helper cell recruitment governed by bystander B cells and ICOS-driven motility. Nature 496:523-527, 2013.
39. 39. Hai Qi^#. From SAP-less T cells to helpless B cells and back: dynamic T-B interactions in germinal center development. Immunological Reviews 247:24-35, 2012.
40. 40. Roza I. Nurieva, Andrew Podd, Yuhong Chen, Andrei M. Alekseev, Mei Yu, Xiaopeng Qi, Hua Huang, Renren Wen, Junmei Wang, Haiyan S. Li, Stephanie S. Watowich, Hai Qi, Chen Dong, and Demin Wang. STAT5 negatively regulates T follicular helper (Tfh) cell generation and function. Journal of Biological Chemistry 287:11234-9, 2012.
41. 41. Yin Liu, Natalya V. Belkina, Chung Park, Raj Nambiar, Scott M. Loughhead, GenaroPatino-Lopez, Khadija Ben-Aissa, Jian-Jiang Hao, Michael J. Kruhlak, Hai Qi, Ulrich H. von Andrian, John H. Kehrl, Matthew J. Tyska, and Stephen Shaw. Constitutively active ezrin increases membrane tension, slows migration, and impedes endothelial transmigration of lymphocytes in vivo in mice. Blood 119:445-453, 2012.
42. 42. Jennifer L. Cannons, Hai Qi, Kristina T. Lu, Mala Dutta, Julio Gomez-Rodriguez, Jun Cheng, Edward K. Wakeland, Ronald N. Germain, and Pamela L. Schwartzberg. Optimal Germinal Center Responses Require A Multistage T Cell: B Cell Adhesion Process Involving Integrins, SLAM-Associated Protein, and CD84. Immunity 32:253, 2010.
43. 43. Frederick Klauschen, Masaru Ishii, Hai Qi, Marc Bajénoff, Jackson G Egen, Ronald N Germain, and Martin Meier-Schellersheim. Quantifying cellular interaction dynamics in 3D fluorescence microscopy data. Nature Protocols 4:1305-11, 2009.
44. 44. Frederick Klauschen, Hai Qi, Jackson G Egen, Ronald N Germain, and Martin Meier-Schellersheim. Computational reconstruction of cell and tissue surfaces for modeling and data analysis. Nature Protocols 4:1006-1012, 2009.
45. 45. Pamela L. Schwartzberg, Kristen L. Mueller, Hai Qi, and Jennifer L. Cannons. SLAM receptors and SAP influence lymphocyte interactions, development and function. Nature Reviews Immunology 9:39-46, 2009.
46. 46. Hai Qi*, Jennifer L. Cannons*, Frederick Klauschen, Pamela L. Schwartzberg, and Ronald N. Germain. SAP-controlled T-B cell interactions underlie germinal centre formation. Nature 455:764-769, 2008. (* co-first authors)
47. 47. Ronald N. Germain, Marc Bajénoff, Flora Castellino, Marcello Chieppa, Jackson G. Egen, Alex Y. C. Huang, Masaru Ishii, Lily Y. Koo, and Hai Qi. Making friends in out-of-the-way places: how cells of the immune system get together and how they conduct their business as revealed by intravital imaging. Immunological Reviews 221:163-181, 2008.
48. 48. Marc Bajénoff, Jackson G. Egen, Hai Qi, Alex Y.C. Huang, Flora Castellino, and Ronald N. Germain. Highways, Byways, and Breadcrumbs: Directing Lymphocyte Traffic in the Lymph Node. Trends in Immunology 28:346-352, 2007.
49. 49. Hai Qi, Jackson G. Egen, Alex Y. C. Huang, and Ronald N. Germain. Extrafollicular activation of lymph node B cells by antigen-bearing dendritic cells. Science 312:1672-1676, 2006.
50. 50. Marc Bajénoff , Béatrice Breart, Alex Y.C. Huang, Hai Qi, Julie Cazareth, Veronique M. Braud, and Ronald N. Germain, Nicolas Glaichenhaus. NK cell behavior in lymph nodes revealed by static and real-time imaging. Journal of Experimental Medicine 203:619-631, 2006.
51. 51. Ronald N. Germain, Flora Castellino, Marcello Chieppa, Jackson G. Egen, Alex Y.C. Huang, Lily Y. Koo, and Hai Qi. An extended vision for dynamic high-resolution intravital immune imaging. Seminars in Immunology 17:431-441, 2005.
52. 52. Alex Y.C. Huang, Hai Qi, and Ronald N. Germain. Illuminating the landscape of in vivo immunity:  insights from dynamic in situ imaging of secondary lymphoid tissues. Immunity 21:331-339, 2004.
53. 53. Hai Qi, JiaxiangJi, Nanchaya Wanasen and Lynn Soong. Enhanced replication of Leishmania amazonensis amastigotes in interferon-g-stimulated murine macrophages: implications for the pathogenesis of cutaneous leishmaniasis. Infection and Immunity 72:988-995, 2004.
54. 54. Timothy L. Denning, Hai Qi, Rolf König, Kevin G. Scott, Makoto Naganuma, and Peter B. Ernst. CD4⁺ Th cells resembling regulatory T cells that inhibit chronic colitis differentiate in the absence of interactions between CD4 and Class II MHC. Journal of Immunology 171:2279-2286, 2003.
55. 55. Hai Qi, Timothy L. Denning, and Lynn Soong. Differential induction of IL-10 and IL-12 in dendritic cells by microbial Toll-Like Receptor activators and the skewing of T cell cytokine profiles. Infection and Immunity 71:3337-3342, 2003.
56. 56. Jiaxiang Ji, Jiaren Sun, Hai Qi, and Lynn Soong. Analysis of T helper cell responses during infection with Leishmania amazonensis. American Journal of Tropical Medicine & Hygiene 66:338-345, 2002.
57. 57. S. Wesley Long, Xiao-Feng Zhang, Hai Qi, Steven Standaert, David H. Walker, and Xue-Jie Yu. Antigenic variation of Ehrlichia chaffeensis resulting from differential expression of the 28-kilodalton protein gene family. Infection and Immunity 70:1824-1831, 2002.
58. 58. Hai Qi, Vsevolod Popov, and Lynn Soong. Leishmania amazonensis-dendritic cell interactions in vitro and the priming of parasite-specific CD4⁺ T cells in vivo. Journal of Immunology 167:4534-4542, 2001.