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| 1 | An antibody against Siglec-15 promotes bone formation and fracture healing by increasing TRAP^(+)mononuclear cells and PDGF-BB secretion显示文摘Osteoporosis(OP)is a common age-related disease characterized by a deterioration of bone mass and structure that predisposes patients to fragility fractures.Pharmaceutical therapies that promote anabolic bone formation in OP patients and OP-induced fracture are needed.We investigated whether a neutralizing antibody against Siglec-15 can simultaneously inhibit bone resorption and stimulate bone formation.We found that the multinucleation of osteoclasts was inhibited in SIGLEC-15 conditional knockout mice and mice undergoing Siglec-15 neutralizing antibody treatment.The secretion of platelet-derived growth factor-BB(PDGF-BB),the number of tartrate-resistant acid phosphatase-positive(TRAP+)mononuclear cells,and bone formation were significantly increased in the SIGLEC-15 conditional knockout mice and antibody-treated mice.The anabolic effect of the Siglec-15 neutralizing antibody on bone formation was blunted in mice with Pdgfb deleted in TRAP-1'cells.These findings showed that the anabolic effect of the Siglec-15 neutralizing antibody was mediated by elevating PDGF-BB production of TRAP4 mononuclear cells.To test the therapeutic potential of the Siglec-15 neutralizing antibody,we injected the antibody in an ovariectomy-induced osteoporotic mouse model,which mimics postmenopausal osteoporosis in women,and in two fracture healing models because fracture is the most serious health consequence of osteoporosis.The Siglec-15 neutralizing antibody effectively reduced bone resorption and stimulated bone formation in estrogen deficiency-induced osteoporosis.Of note,the Siglec-15 neutralizing antibody promoted intramembranous and endochondral ossification at the damaged area of cortical bone in fracture healing mouse models.Thus,the Siglec-15 neutralizing antibody shows significant translational potential as a novel therapy for OP and bone fracture. | Gehua Zhen Yang Dan Ruomei Wang Ce Dou Qiaoyue Guo Melissa Zarr Linda N.Liu Lieping Chen Ruoxian Deng Yusheng Li Zengwu Shao Xu Cao | 2021 | Bone Research2021，9，4： | 6 |
| 2 | B7-DC (PD-L2) costimulation of CD4^(+) T-helper 1 response via RGMb显示文摘The role of B7-DC in T-cell responses remains controversial because both coinhibitory and costimulatory functions have been reported in various experimental systems in vitro and in vivo.In addition to interacting with the coinhibitory receptor PD-1,B7-DC has also been shown to bind repulsive guidance molecule b(RGMb).The functional consequences of the B7-DC/RGMb interaction,however,remain unclear.More than a decade ago,we reported that replacement of a murine B7-DC mutant lysine with serine(K113S)at positive 113 resulted in a loss of binding capacity to PD-1.Nevertheless,K113S remained costimulatory for T cells in vitro,implicating a dual functionality for B7-DC in T-cell responses.Here we show that recombinant K113S protein interacts with RGMb with a similar affinity to wild-type B7-DC.More importantly,K113S costimulates CD4^(+)T-cell responses via RGMb and promotes Th1 polarization.RGMb is expressed on the surface of naive mouse T cells,macrophages,neutrophils and dendritic cells.Finally,K113S/RGMb costimulation suppresses Th2-mediated asthma and ameliorates small airway inflammation and lung pathology in an experimental mouse model.Our findings indicate that RGMb is a costimulatory receptor for B7-DC.These findings from the K113S variant provide not only a possible explanation for the B7-DC-triggered contradictory effects on T-cell responses,but also a novel approach to investigate the B7-DC/PD-1/RGMb axis.Recombinant K113S or its derivatives could potentially be developed as an agonist for RGMb to costimulate the Th1 response without triggering PD-1-mediated T-cell inhibition. | Xinxin Nie Wenni Chen Ying Zhu Baozhu Huang Weiwei Yu Zhanshuai Wu Sizheng Guo Yiping Zhu Liqun Luo Shengdian Wang Lieping Chen | 2018 | Cellular & Molecular Immunology2018，15，10： | 3 |
| 3 | Anti-PD-1/PD-L1 therapy of human cancer: past, present, and future显示文摘 | Chen Lieping Han Xue | 2015 | Journal of Clinical Investigation2015，，9： | 2 |
| 4 | Co-inhibitory molecules of the B7-CD28 family in the control of T-cell immunity显示文摘 | Lieping Chen | 2004 | Nat Rev Immunol2004，4，5： | 1 |
| 5 | B7-H4, a Molecule of the B7 Family, Negatively Regulates T Cell Immunity显示文摘 | Gabriel L Sica In-Hak Choi Gefeng Zhu Koji Tamada Sheng-Dian Wang Hideto Tamura Andrei I Chapoval Dallas B Flies Jürgen Bajorath Lieping Chen | 2003 | Immunity2003，，： | 1 |
| 6 | Co inhibitory molecules of the B7 - CD28 family in the control of T cell immunity 显示文摘 | Chen Lieping | 2004 | Nature Reviews Immunology2004，4，5： | 1 |
| 7 | The growth of private hospitals and their health workforce in Chi- na: a comparison with public hospitals 显示文摘 | Tang Chengxiang Zhang Yucheng Chen Lieping | 2014 | Health Policy Plan2014，，29： | 1 |
| 8 | The growth of private hospitals and their health workforce in China:a comparison with public hospitals显示文摘 | Tang Chengxiang Zhang Yucheng Chen Lieping | 2014 | Health Policy Plan2014，29，： | 1 |
| 9 | Local Expression of B7-H4 by Recombinant Adenovirus Transduction in Mouse Islets Prolongs Allograft Survival显示文摘 | Xiaojie Wang Jianqiang Hao Daniel L. Metzger Alice Mui Ziliang Ao C Bruce Verchere Lieping Chen Dawei Ou Garth L. Warnock | 2009 | Transplantation2009，，4： | 1 |
| 10 | Human papillomavirus type 16 nucleoprotein E7 is a tumor rejection antigen显示文摘 | Lieping Chen Elaine Linnoy Thomas | 1991 | Proc Natl Acad Sci USA1991，88，： | 1 |
| 11 | B7-H4.Ig inhibits the development of Type 1 diabetes by regulating Th17 cells in NOD mice显示文摘 | I-Fang Lee Xiaojie Wang Jianqiang Hao Noushin Akhoundsadegh Lieping Chen Linda Liu Sol Langermann Dawei Ou Garth L. Warnock | 2013 | Cellular Immunology2013，，1： | 1 |
| 12 | A crucial role of the PD-1H coinhibitory receptor in suppressing experimental asthma显示文摘Programmed death one homolog (PD-1H) is a cell surface molecule of the B7/CD28 immune modulatory genefamily. Although PD-1H has been shown to function as a coinhibitory receptor on T cells to limit naive T-cellactivation and proliferation, its role in the regulation of the T-cell response to allergens is unknown. We report herethat genetic ablation or blockade of PD-1H drastically promotes pulmonary inflammation with massive accumulationof eosinophils in a mouse model of experimental asthma, indicating a suppressive function of PD-1H in allergicinflammation. The loss of PD-1H led to elevated production of both innate cytokines (IL-6, MCP-1 and TNFα) andTh2 cytokines (IL-5 and IL-13) in the lung, indicating a critical role of PD-1H in suppressing the production ofairway inflammatory cytokines. In addition, the loss of PD-1H also impaired the expansion of systemic andpulmonary regulatory T cells during asthma induction. These findings support a critical role of intrinsic PD-1H inthe regulation of inflammatory responses to allergens. Finally, we showed that treatment with a PD-1H agonisticmonoclonal antibody reduced the severity of asthma, which was accompanied by suppressed lung inflammation.Our findings support PD-1H as a potential target and suggest a possible strategy for the treatment of allergicasthma in humans. | Huafeng Liu Xin Li Li Hu Min Zhu Bailin He Liqun Luo Lieping Chen | 2018 | Cellular & Molecular Immunology2018，15，9： | 1 |
| 13 | B7-H4, a Molecule of the B7 Family, Negatively Regulates T Cell Immunity显示文摘 | Gabriel L Sica In-Hak Choi Gefeng Zhu Koji Tamada Sheng-Dian Wang Hideto Tamura Andrei I Chapoval Dallas B Flies Jürgen Bajorath Lieping Chen | 2003 | Immunity2003，，6： | 1 |
| 14 | B7-H1 Determines Accumulation and Deletion of Intrahepatic CD8 + T Lymphocytes显示文摘 | Haidong Dong Gefeng Zhu Koji Tamada Dallas B. Flies Jan M.A. van Deursen Lieping Chen | 2004 | Immunity2004，，3： | 1 |
| 15 | B7-H1 pathway and its role in the evasion of tumor immunity显示文摘 | Haidong Dong Lieping Chen | 2003 | Journal of Molecular Medicine2003，，5： | 1 |
| 16 | B7-H1 pathway and its role in the evasion of tumor immunity显示文摘 | Haidong Dong Lieping Chen | 2003 | Journal of Molecular Medicine2003，，5： | 1 |
| 17 | The development and functions of CD41 T cells expressing a transgenic TCR specific for an MHC-I-restricted tumor antigenic epitope显示文摘It has been reported that the ratio of CD41 to CD81 T cells has no bias in a few class I major histocompatibility complex(MHC-I)-restricted T-cell receptor(TCR)-transgenic mice specific for alloantigens or autoantigens,in which most CD41 T cells express an MHC-I-restricted TCR.In this study,we further showed that more than 50%of CD41 T cells in MHC-I-restricted P1A tumor antigen-specific TCR(P1ATCR)-transgenic mice could specifically bind to MHC-I/P1A peptide complex.P1A peptide could stimulate the transgenic CD41 T cells to proliferate and secrete both type 1 helper T cell and type 2 helper T cell cytokines.The activated CD41 T cells also showed cytotoxicity against P1A-expressing tumor cells.The analysis of TCR a-chains showed that these CD41 T cells were selected by co-expressing endogenous TCRs.Our results show that CD41 T cells from P1ATCR transgenic mice co-expressed an MHC-I-restricted transgenic TCR and another rearranged endogenous TCRs,both of which were functional. | Xue Han Peiying Ye Liqun Luo Linghua Zheng Yang Liu Lieping Chen Shengdian Wang | 2011 | Cellular & Molecular Immunology2011，8，4： | 0 |
| 18 | Author Correction:A crucial role of the PD-1H coinhibitory receptor in suppressing experimental asthma显示文摘In the Acknowledgement section of this article,NIH grants numbered P50 CA196530 and P30 CA016359 were incorrectly attributed to author Lieping Chen and should not have been cited.The original article has been corrected. | Huafeng Liu Xin Li Li Hu Min Zhu Bailin He Liqun Luo Lieping Chen | 2023 | Cellular & Molecular Immunology2023，20，7： | 0 |
| 19 | Anti-TOSO antibody treatment promotes T cell activation-induced cell death(AICD) in vitro and in vivo显示文摘T cell activation-induced cell death(AICD),that involves the induction of Fas-mediated apoptosis,is very important for the maintenance of immune homeostasis.TOSO was firstly described as an inhibitor of Fasmediated apoptosis and overexpressed in chronic lymphocytic leukemia.Recently,TOSO was identified as IgM FcR.In this study,we produced anti-TOSO monoclonal antibody(mAb)that could block the binding of IgM to TOSO and found that T cell apoptosis is negatively correlated with TOSO expression during T cell activation.Treatment of activated T cells with anti-TOSO blocking mAb promoted T cell AICD in in vitro AICD model,and treatment of xenogeneic-GVHD mice with the antibody also increased the sensitivity of activated T cells to Fasinduced apoptosis,which was accompanied by reduction of c-FLIPL expression and up-regulation of AP-1 complex.In summary,our data indicate the anti-apoptotic effect of TOSO in T cell AICD and open up new therapeutic prospects for the treatment of hematologic malignancies and immune disorders. | Yi Tan Xue Han Xiaoran Wu Qiao Xing Lieping Chen Shengdian Wang | 2014 | Chinese Science Bulletin2014，59，13： | 0 |
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