Profile

Laboratory of immune Regulation, Institute of Immunology

Zhejiang University School of Medicine

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Research Interests

The main focus of our lab is to elucidate the molecular pathways and cellular interactions that mediate and regulate thymocyte development and T cell-mediated immune responses by using molecular biology and genetic approaches. We are especially interested in the identification and characterization of novel immune-related molecules, and the development and treatment of cancer  and autoimmune diseases.

Main approaches

Molecular biology approaches, gene knock-out, cell culture, mouse model of autoimmune diseases


1. CD8 cells in immune regulation and development of autoimmune diseases CD8+ regulatory T cells play key roles in maintaining self-tolerance. We have been focused on the study of Qa1-restricted CD8+ regulatory cells in mice. We have discovered that the suppressive activity of these regulatory cells was tightly regulated by the interaction of CD94/NKG2A and Qa1. Disruption of the CD94/NKG2A-Qa1 by either site-directed mutagenesis or antibody blockade enables the maximum release of NK and CD8+ suppressive activity and amelioration of autoimmune diseases such as EAE in miceLu et al. Immunity 2007, PNAS 2008We have recently reported that Glatiramer acetate, a FDA proved anti-MS drug, was able to induce Qa1-resricted CD8+ regulatory cells in mice, which could be used for the treatment of autoimmune IBDYao Y et al. Eur. J. Immunol. 2013. We are currently exploring the role of CD8 subpopulations in anti-tumor and anti-viral responses. We are also interested in the equivalent subpopulation of CD8 regulatory cells in human and its relevance to human autoimmune and infectious diseases.

2. Thymocyte development and immune cell signalingProgrammed gene expression is critical for T-lineage cell differentiation as well as cell activation upon stimulation. We’ve analyzed the gene expression profile during thymocyte development in the thymus and identified an important adaptor protein Tespa1 (Wang et al. Nature Immunology 2012). Further analysis revealed that this molecule associates with TCR signaling components PLC-g1 and Grb2, and contributes to the activation of the Ca2+/NFAT pathways upon TCR engagement. We are currently investigating the molecular mechanisms how Tespa1 regulates TCR signaling as well as the role of some other important signaling molecules in regulating this development process.

 

3. Integrative signaling in Regulation of TH17 cell differentiation: TH17 cells (interleukin-17-producing helper T cells) are present at the sites of tissue inflam­mation and associated with the induction of multiple autoimmune diseases. The differentiation of TH17 cells is instructed and critically regulated by various cytokines in the microenvironment, which drive intracellular signaling process and transcription profiles that determine the cell fate. In our study, we found that MINK1, a germinal center kinase (GCK) family kinase, plays as a negative regulator for TH17 cell differentiation. We are currently investigating the mechanisms of this regulation.

PI Profile

Prof. Linrong Lu

Institute of Immunology

Zhejiang University School of Medicine

E-mail: lu_linrong@zju.edu.cn

 

BIOGRAPHY

1988-1993    BA  USTC, Hefei, China (Molecular Biology)

1993-1998    PhD Shanghai Institute of Biochemistry, CAS, Shanghai, China

1998-2001    Postdoctoral Associate, MIT-HST, Cambridge MA

2001-2008    Research Scientist, DFCI Harvard Medical School, Boston MA

2008-present  Professor, Zhejiang University School of Medicine, Hangzhou, China

2014-present  Vice Dean, ZJU-UoE Institute, Zhejiang Univrsity, Hangzhou, China

 

SELECTED PUBLICATIONS

1. Fu G, Xu Q, Qiu Y, Jin X, Xu T, Dong S, Wang J, Ke Y, Hu H, Cao X, Wang D, Cantor H, Gao X, Lu L*. Suppression of TH17 cell differentiation and autoreactive inflammatory response by Misshapen/NIK-related kinase MINK1. J Exp. Med. 2017 (Accepted)

2. Yue M, Luo D, Yu S, Liu P, Zhou Q, Hu M, Liu Y, Wang S, Huang Q, Niu Y, Lu L*, Hu H*. Misshapen/ NIK-related Kinase (MINK1) is involved in platelet function, hemostasis and thrombus formation. Blood. 2016 Feb;127 (7): 927-37.

3. Wang D, Zheng M, Qiu Y, Guo C, Ji J, Lei L, Zhang X, Liang J, Lou J, Huang W, Dong B, Wu S, Wang J, Ke Y, Cao X, Zhou YT and Lu L*, Tespa1 negatively regulates FcεRI-mediated signaling and the mast cell-mediated allergic response. J Exp. Med. 2014 Dec 15;211(13):2635-49.

4. Yao Y, Han W, Liang J, Ji Jian, Wan J, Cantor H, Lu L*, Glatiramer acetate ameliorates inflammatory bowel disease in mice through the induction of Qa-1-restricted CD8+ regulatory cells. Eur. J. Immunol. 2013, 43:125-36.

5.    Wang D, Zheng M, Lei L, Ji J, Yao Y, Qiu Y, Ma L, Lou J, Ouyang C, Zhang X, He Y, Chi J, Wang L, Kuang Y, Wang J, Cao X and Lu L*, Tespa1 is involved in late thymocyte development through the regulation of TCR-mediated signaling. Nature Immunology 2012, 13: 560–68.

6.    Wang D Lou J, Ouyang C Chen W Liu Y Liu X Cao X Wang J and Lu L*, Ras-related protein Rab10 facilitates TLR4 signaling by promoting replenishment of TLR4 onto the plasma membrane. Proc Natl Acad Sci U S A. 2010, 107:13806-11.

7.    Kim HJ, Verbinnen B, Tang X, Lu L, and Cantor H*, Inhibition of follicular T helper cells by CD8+ Treg is essential for self-tolerance. Nature. 2010 Sep 16;467(7313):328-32.

8.    Lu L, Kim H-J, Werneck M and Cantor H*, Regulation of CD8+ Treg: Interruption of NKG2A- Qa-1 interaction allows robust suppressive activity and resolution of autoimmune disease. Proc Natl Acad Sci U S A. 2008, 105:19420-5.

9.    Lu L, Ikizawa K, Hu D, Werneck MBF, Wucherpfennig KW, and Cantor H*., Regulation of Activated CD4+ T Cells by NK Cells via the Qa-1–NKG2A Inhibitory Pathway, Immunity 2007,25(5): 593-604.