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| 1 | Generation and Regulation of CD8^+ Regulatory T Cells显示文摘Research into the suppressive activity of CD4+FoxP3+ T regulatory cells (Treg) has defined a sublineage of CD4+ cells that contribute to self-tolerance and resistance to autoimmune disease. Much less attention has been given to the potential contribution of regulatory sublineages of CD8+ cells. Analysis of a small fraction of CD8+ cells that target autoreactive CD4+ cells through recognition of the MHC class Ib molecule Qa-1 in mouse and HLA-E in human has revitalized interest in CD8+ Treg. Here we summarize recent progress and future directions of research into the role of this CD8+ sublineage in resistance to autoimmune disease. | Linrong Lu Harvey Cantor | 2008 | Cellular & Molecular Immunology2008，5，6： | 22 |
| 2 | Therapeutic efficacy of anti-CD19 CAR-T cells in a mouse model of systemic lupus erythematosus显示文摘Dysregulated B-cell activation plays pivotal roles in systemic lupus erythematosus(SLE),which makes B-cell depletion a potential strategy for SLE treatment.The clinical success of anti-CD19 CAR-T cells in treating B-cell malignancies has attracted the attention of researchers.In this study,we aimed to investigate the feasibility of applying anti-CD19 CAR-T cell therapy to SLE treatment in a mouse disease model.We constructed murine anti-CD19 CARs with either CD28 or 4-1BB as the intracellular costimulatory motif and evaluated the therapeutic function of the corresponding CAR-T cells by infusing them into MRL-lpr mice.Furthermore,anti-CD19 CAR-T cells were transferred to MRL-lpr mice before the onset of disease to determine their role in SLE prevention.According to our observations,compared with antibody treatment,the adoptive transfer of our anti-CD19 CAR-T cells showed a more sustained B-cell-depletion effect in MRL-lpr mice.The transfer of syngeneic anti-CD19 CAR-T cells not only prevented disease pathogenesis before the onset of disease symptoms but also displayed therapeutic benefits at a later stage after disease progression.We also tried to optimize the treatment strategy and found that compared with CAR-T cells with the CD28 costimulatory motif,CAR-T cells with the 4-1BB costimulatory motif showed better therapeutic efficiency without cell enrichment.Taken together,these results show that anti-CD19 CAR-T cell therapy was effective in the prevention and treatment of a murine model of SLE,indicating its potential for clinical use in patients. | Xuexiao Jin Qin Xu Chengfei Pu Kaixiang Zhu Cheng Lu Yu Jiang Lei Xiao Yongmei Han Linrong Lu | 2021 | Cellular & Molecular Immunology2021，18，8： | 12 |
| 3 | Scaffolding protein Gab1 regulates myeloid dendritic cell migration in allergic asthma显示文摘气喘是在多重基因、环境的因素之中包含复杂相互影响的普通过敏混乱。最近的研究作为一个新奇气喘危险性因素识别了人的 GAB1 的基因变体。然而,在肺的 Gab1 的功能仍然保持大部分未经勘探。在这研究,我们首先在尖锐恶化期间从气喘的病人在外部血 mononuclear 房间观察了 Gab1 水平的举起与康复相比。有在 myeloid 的有选择地破坏的 Gab1 的老鼠树枝状的房间(mDCs ) 更加在气喘的试验性的模型稀释了过敏发炎。进一步的调查在 Gab1 缺乏的 mDCs 的调停 CCL19 的移植揭示了突出的减小到排干淋巴节点和驾驶 Th2 的适应激活的随后的缺陷。机械学地, Gab1 是在气喘的回答期间调整 mDC 移植的 CCL19/CCR7 chemokine 轴的一个必要部件。一起,这些调查结果在肺为 Gab1 的角色提供第一条证据,给我们气喘的致病的更深的理解。 | Yun Zhang Yun Xu Shuwan Liu Xiaohong Guo Dong Cen Jiaqi Xu Heyuan Li Kaijun Li Chunlai Zeng Linrong LU Yiting Zhou Huahao Shen Hongqiang Cheng Xue Zhang Yuehai Ke | 2016 | Cell Research2016，26，11： | 3 |
| 4 | Priming of NLRP3 inflammasome activation by Msn kinase MINK1 in macrophages显示文摘The nucleotide-binding domain,leucine-rich-repeat containing family,pyrin domain-containing 3(NLRP3)inflammasome is essential in inflammation and inflammatory disorders.Phosphorylation at various sites on NLRP3 differentially regulates inflammasome activation.The Ser725 phosphorylation site on NLRP3 is depicted in multiple inflammasome activation scenarios,but the importance and regulation of this site has not been clarified.The present study revealed that the phosphorylation of Ser725 was an essential step for the priming of the NLRP3 inflammasome in macrophages.We also showed that Ser725 was directly phosphorylated by misshapen(Msn)/NIK-related kinase 1(MINK1),depending on the direct interaction between MINK1 and the NLRP3 LRR domain.MINK1 deficiency reduced NLRP3 activation and suppressed inflammatory responses in mouse models of acute sepsis and peritonitis.Reactive oxygen species(ROS)upregulated the kinase activity of MINK1 and subsequently promoted inflammasome priming via NLRP3 Ser725 phosphorylation.Eliminating ROS suppressed NLRP3 activation and reduced sepsis and peritonitis symptoms in a MINK1-dependent manner.Altogether,our study reveals a direct regulation of the NLRP3 inflammasome by Msn family kinase MINK1 and suggests that modulation of MINK1 activity is a potential intervention strategy for inflammasomerelated diseases. | Kaixiang Zhu Xuexiao Jin Zhexu Chi Sheng Chen Songquan Wu Richard D.Sloan Xuai Lin Dante Neculai Di Wang Hu Hu Linrong Lu | 2021 | Cellular & Molecular Immunology2021，18，10： | 2 |
| 5 | CD4+T cells memorize obesity and promote weight regain显示文摘Body weight regain often causes failure of obesity therapies while the underlying mechanism remains largely unknown.In this study,we report that immune cells,especially CD4+T cells,mediate the‘memory’of previous obese status.In a weight gain-loss-regain model,we found that C57BL/6J mice with an obesity history showed a much faster rate of body weight regain.This obesity memory could last for at least 2 months after previously obese mice were kept at the same body weight as non-obese mice.Surprisingly,such obesity memory was abrogated by dexamethasone treatment,whereas immunodeficient Rag1−/−and H2A−/−mice failed to establish such memory.Rag1−/−mice repossessed the obesity memory when immune cells or CD4+T cells isolated from previously obese mice were transferred.Furthermore,depletion of CD4+T cells led to obesity memory ablation.Taken together,we conclude that CD4+T cells mediate obesity memory and promote weight regain. | Jianghuan Zou Beibei Lai Mingzhu Zheng Qin Chen Shujun Jiang Anying Song Zan Huang Peiliang Shi Xin Tu Di Wang Linrong Lu Zhaoyu Lin Xiang Gao | 2018 | Cellular & Molecular Immunology2018，15，6： | 2 |
| 6 | JAK3 mediates c-myc gene expression induced by interleukin-2显示文摘C myc gene expression can be rapidly induced by IL 2 through intracellular signal transduction which is triggered by the interaction between IL 2 and its receptor (IL 2R). JAK3 which associates to the intracellular domain of IL2R γ may play a critical role in this process. To reveal the action of JAK3 in c myc induction, a chimeric receptor gene IL2R α/γ/Δ NJAK3 is constructed which consists of extracellular domain derived from IL 2R α subunit (IL2R α), the transmembrane sequence derived from IL2R γ and the cytoplasmic domain derived from the catalytic domain of JAK3 (Δ NJAK3), and then transfected this chimeric gene into mouse fibroblast cell line L929 β which had been transfected with IL2R β gene and stably expressed IL2R β in high level. In the transfectants coexpressing IL2R β and α/γ/Δ NJAK3, the stimulation of IL2 could intensively induce c myc gene expression. Because the whole cytoplasmic domain of IL2R γ which could recruit signaling molecules was replaced by JAK3 and the c myc could be still induced by IL2 in this situation, the results here gave the direct evidence demonstrating that JAK3 plays an important role in c myc gene expression induced by IL2. | Zhu Jinfang Lu Linrong Ji Hongbin Zheng Zhongcheng J. Thèze Liu Xinyuan | 1998 | Chinese Science Bulletin1998，43，4： | 1 |
| 7 | miR-409-3p inhibits HT1080 cell proliferation, vascularization and metastasis by targeting angiogenin显示文摘 | Chunhua Weng Haojie Dong Guangdi Chen Yixing Zhai Rongpan Bai Hu Hu Linrong Lu Zhengping Xu | 2012 | Cancer Letters2012，，2： | 1 |
| 8 | One way to pathogenesis, many ways to homeostasis显示文摘 | Linrong Lu Jianli Wang | 2013 | Cellular & Molecular Immunology2013，10，1： | 0 |
| 9 | Flexible organic electrochemical transistors for chemical and biological sensing显示文摘Chemical and biological sensing play important roles in healthcare,environmental science,food-safety tests,and medical applications.Flexible organic electrochemical transistors(OECTs)have shown great promise in the field of chemical and biological sensing,owing to their superior sensitivity,high biocompatibility,low cost,and light weight.Herein,we summarize recent progress in the fabrication of flexible OECTs and their applications in chemical and biological sensing.We start with a brief introduction to the working principle,configuration,and sensing mechanism of the flexible OECT-based sensors.Then,we focus on the fabrication of flexible OECT-based sensors,including material selection and structural engineering of the components in OECTs:the substrate,electrodes,electrolyte,and channel.Particularly,the gate modification is discussed extensively.Then,the applications of OECT-based sensors in chemical and biological sensing are reviewed in detail.Especially,the array-based and integrated OECT sensors are also introduced.Finally,we present the conclusions and remaining challenges in the field of flexible OECT-based sensing.Our timely review will deepen the understanding of the flexible OECT-based sensors and promote the further development of the fast-growing field of flexible sensing. | Li Wang Xiaoping Yue Qizeng Sun Linrong Zhang Guozhang Ren Gang Lu Hai-Dong Yu Wei Huang | 2022 | Nano Research2022，15，3： | 0 |
| 10 | 胆酸通过抑制NLRP3炎症小体活化控制炎症及代谢综合征的发生显示文摘免疫系统和代谢系统的相互作用彼此影响着对方生理功能的正常发挥,对于维持机体的代谢平衡和免疫稳态起着重要的调节作用。当二者的相互调控出现失衡或发生异常时,往往会导致机体相关病理性事件如代谢综合征、自身免疫性疾病、心血管疾病以及肿瘤等的发生。 | Chuansheng Guo Shujun Xie Zhexu Chi Jinhua Zhang Yangyang Liu Li Zhang Mingzhu Zheng Xue Zhang Dajing Xia Yuehai Ke Linrong Lu 王迪 | 2017 | 科学新闻2017，19，4： | 0 |
| 11 | CAR-T cell therapy: new hope for systemic lupus erythematosus patients显示文摘In a recent study from NEJM,Mougiakakos et al.reported a case in which autologous anti-CD19 CAR-T cell therapy was used in the treatment of a refractory SLE patient[1].Rapid remission of severe SLE was observed in this case,indicating the potential of application of B cell-targeting CAR-T cell therapy in severe autoimmune diseases. | Xuexiao Jin Yongmei Han James Q.Wang Linrong Lu | 2021 | Cellular & Molecular Immunology2021，18，12： | 0 |
| 12 | Activated mouse CD4+Foxp3- T cells facilitate melanoma metastasis via Qa-1-dependent suppression of NK-cell cytotoxicity显示文摘 | Xiaojuan Wang Yanyan Cui Gaoxmg Luo Qinghong Wang Jie Hu Weifeng He Jun Yuan Junyi Zhou Yan Wu Xiaofeng Sun Simon C Robson Xianchang Li Jiangling Tan Yanmeng Peng Gang Xue Linrong Lu Wenda Gao Jun Wu | 2012 | Cell Research2012，22，12： | 0 |
| 13 | Thymic-specific regulation of TCR signaling by Tespa1显示文摘Double-positive(DP)thymocytes undergo positive selection to become mature single-positive CD4+and CD8+T cells in response to T cell receptor(TCR)signaling.Unlike mature T cells,DP cells must respond to low-affinity self-peptide-MHC ligands before full upregulation of their surface TCR expression can occur.Thus,DP thymocytes must be more sensitive to ligands than mature T cells.A number of molecules have been found that are able to enhance the strength of the TCR signal to facilitate positive selection.However,almost all of these molecules are also active in mature T cells.Themis(thymocyte expressed molecule involved in selection)and Tespa1(thymocyte expressed positive selection associated 1)are two recently discovered molecules essential for optimal TCR signaling and thymocyte development.A deficiency in both molecules leads to defects in positive selection.Here,we compared the relative contributions of Themis and Tespa1 to positive selection in thymocytes.We show that Tespa1 deficiency led to more limited and specific gene expression profile changes in cells undergoing positive selection.In mixed bone marrow transfer experiments,Tespa1^(−/−)cells showed more severe defects in thymocyte development than Themis^(−/−)cells.However,Tespa1^(−/−)cells showed a substantial degree of homeostatic expansion and became predominant in the peripheral lymphoid organs,suggesting that Tespa1 is a thymic-specific TCR signaling regulator.This hypothesis is further supported by our observations in Tespa1 conditional knockout mice,as Tespa1 deletion in peripheral T cells did not affect TCR signaling or cell proliferation.The different regulatory effects of Tespa1 and Themis are in accordance with their nonredundant roles in thymocyte selection,during which Tespa1 and Themis double knockouts showed additive defects. | Jun Lyu Pengfei Wang Ting Xu Yichao Shen Zejin Cui Mingzhu Zheng Guo Fu Linrong Lu | 2019 | Cellular & Molecular Immunology2019，16，12： | 0 |
| 14 | Mobilizing ER IP3 receptors as a mechanism to enhance calcium signaling显示文摘Calcium is an important cell signaling intermediate known to play a critical role in T-cell receptor(TCR)-mediated activation of both developing thymocytes and mature peripheral T cells.Upon antigen engagement,the TCR recruits PLCγ1 to the proximal signaling complex to be phosphorylated and activated by the membrane-bound kinase Itk.Activated PLCγ1 mediates the cleavage of the cell membrane lipid component PIP2 into the lipids diacylglycerol(DAG)and inositol 1,4,5-triphosphate(IP3). | Linrong Lu | 2021 | Cellular & Molecular Immunology2021，18，9： | 0 |
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