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CD40-activated B cells are more potent than immature dendritic cells to induce and expand CD41 regulatory T cells

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Cellular & Molecular Immunology 2010年第1期7卷 44-50页

作者： Jian Zheng Yinping Liu yu-lung lau Wenwei Tu Department of Paediatrics and Adolescent Medicine Li Ka Shing Faculty of MedicineUniversity of Hong KongHong KongChina Joint Research Centre West China Second University HospitalSichuan University and Faculty of MedicineUniversity of Hong KongChengduChina

CD4^(+)regulatory T cells(Tregs)play an important role in maintaining immune tolerance by suppressing pathologic immune responses.,The generation of large numbers of antigen-specific Tregs ex vivo is critical for the development of clinical immunotherapy based on the adoptive transfer of *** CD40-activated B cells(CD40-B)and immature dendritic cells(imDCs)have been used as professional antigen-presenting cells(APCs)to generate antigen-specific ***,the efficiencies of CD40-B and imDCs to generate CD4^(+)Tregs have not been compared directly and the mechanism driving the generation of these Tregs remains largely *** this study,we found that CD40-B exhibited mature phenotypes and were more able to induce and expand CD4^(high)"CD25^(+)Tregs than ***,Tregs induced by CD40-B had greater suppressive capacity than those induced by *** generation of CD4^(high)CD25^(+)Tregs by CD40-B and imDCs is cell-cell contact dependent and partially relies on the expression of human leukocyte antigen(HLA)-DR and CD80/*** in CD4^(high)CD25^(+)Treg generation efficiency were largely explained by the production of endogenous IL-2 by *** results suggest that CD40-B is better able to generate large numbers of antigen-specific Tregs than ***,using CD40-B to generate Tregs may accelerate the clinical use of Treg-based immunotherapy in the treatment of allograft rejection,graft versus host disease(GVHD)and autoimmune diseases.

关键词： B cells immature DC Treg IL-2

In-depth cDNA Library Sequencing Provides Quantitative Gene Expression Profiling in Cancer Biomarker Discovery

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Genomics, Proteomics & Bioinformatics 2009年第1期7卷 1-12页

作者： Wanling Yang Dingge Ying yu-lung lau Department of Paediatrics and Adolescent Medicine LKS Faculty of Medicine The University of Hong Kong Hong Kong China

Quantitative gene expression analysis plays an important role in identifying differentially expressed genes in various pathological states, gene expression regulation and co-regulation, shedding light on gene functions. Although microarray is widely used as a powerful tool in this regard, it is suboptimal quantitatively and unable to detect unknown gene variants. Here we demonstrated effective detection of differential expression and co-regulation of certain genes by expressed sequence tag analysis using a selected subset of cDNA libraries. We discussed the issues of sequencing depth and library preparation, and propose that increased sequencing depth and improved preparation procedures may allow detection of many expression features for less abundant gene variants. With the reduction of sequencing cost and the emerging of new generation sequencing technology, in-depth sequencing of cDNA pools or libraries may represent a better and powerful tool in gene expression profiling and cancer biomarker detection. We also propose using sequence-specific subtraction to remove hundreds of the most abundant housekeeping genes to increase sequencing depth without affecting relative expression ratio of other genes, as transcripts from as few as 300 most abundantly expressed genes constitute about 20% of the total transcriptome. In-depth sequencing also represents a unique advantage of detecting unknown forms of transcripts, such as alternative splicing variants, fusion genes, and regulatory RNAs, as well as detecting mutations and polymorphisms that may play important roles in disease pathogenesis.

关键词： cDNA sequencing sequencing depth expressed sequence tag sequence-specific subtraction,biomarker,mutation detection

Variable outcome in infantile-onset inflammatory bowel disease in an Asian cohort

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World Journal of Gastroenterology 2016年第48期22卷 10653-10662页

作者： Way Seah Lee Ruey Terng Ng Koon-Wing Chan yu-lung lau Department of Paediatrics University Malaya Medical Center University Malaya Paediatric and Child Health Research Group University Malaya Department of Paediatrics and Adolescent Medicine Queen Mary Hospital LKS Faculty of Medicine The University of Hong Kong

AIM Infantile-onset inflammatory bowel disease(IO-IBD) with the onset of disease before 12 mo of age, is a different disease entity from childhood IBD. We aimed to describe the clinical features, outcome and role of mutation in interleukin-10(IL-10) and interleukin-10 receptors(IL-10R) in Asian children with IO-IBD. METHODS All cases of IO-IBD, defined as onset of disease before 12 mo of age, seen at University Malaya Medical Center, Malaysia were reviewed. We performed mutational analysis for IL10 and IL10 R genes in patients with presenting clinical features of Crohn's disease(CD).RESULTS Six [13%; CD = 3, ulcerative colitis(UC) = 2, IBDunclassified(IBD-U) = 1] of the 48 children(CD = 25; UC = 23) with IBD have IO-IBD. At final review [median(range) duration of follow-up: 6.5(3.0-20) years], three patients were in remission without immunosuppression [one each for post-colostomy(IBD-U), after standard immunosuppression(CD), and after total colectomy(UC)]. Three patients were on immunosuppression:one(UC) was in remission while two(both CD) had persistent disease. As compared with later-onset disease, IO-IBD were more likely to present with bloody diarrhea(100% vs 55%, P = 0.039) but were similar in terms of an associated autoimmune liver disease(0% vs 19%, P = 0.31), requiring biologics therapy(50% vs 36%, P = 0.40), surgery(50% vs 29%, P = 0.27), or achieving remission(50% vs 64%, P = 0.40). No mutations in either IL10 or IL10 R in the three patients with CD and the only patient with IBD-U were *** The clinical features of IO-IBD in this Asian cohort of children who were negative for IL-10 or IL-10 R mutations were variable. As compared to childhood IBD with onset of disease after 12 mo of age, IO-IBD achieved remission at a similar rate.

关键词： Infantile-onset inflammatory bowel disease Pediatric

yδ-T cells： an unpolished sword in human anti-infection immunity

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Cellular & Molecular Immunology 2013年第1期10卷 50-57页

作者： Jian Zheng Yinping Liu yu-lung lau Wenwei Tu Department of Pediatrics and Adolescent Medicine Li Ka Shing Faculty of Medicine University of Hong Kong Hong Kong SAR China

yδ-T cells represent a small population of immune cells, but play an indispensable role in host defenses against exogenous pathogens, immune surveillance of endogenous pathogenesis and even homeostasis of the immune system. Activation and expansion of yδ-T cells are generally observed in diverse human infectious diseases and correlate with their progression and prognosis, yδ-T cells have both ＇innate＇ and ＇adaptive＇ characteristics in the immune response, and their *** activities are mediated by multiple pathways that are under elaborate regulation by other immune components. In this review, we summarize the current state of the literature and the recent advancements in yδ-T cell-mediated immune responses against common human infectious pathogens. Although further investigation is needed to improve our understanding of the characteristics of different yδ-T cell subpopulations under specific conditions, yδ-T cell-based therapy has great potential for the treatment of infectious diseases.

关键词： yδ-T cells infection immunity human

Uncompromised NK cell activation is essential for virus-specific CTL activity during acute influenza virus infection

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Cellular & Molecular Immunology 2018年第9期15卷 827-837页

作者： yuan Liu Jian Zheng Yinping Liu Liyan Wen Lei Huang Zheng Xiang Kwok-Tai Lam Aizhen Lv Huawei Mao yu-lung lau Wenwei Tu Department of Pediatrics and Adolescent Medicine Li Ka Shing Faculty of MedicineThe University of Hong KongHong KongChina Medical Genetic Center Guangdong Women and Children HospitalGuangzhou 511400China Department of Radiology Georgia Regents UniversityAugustaGA 30912USA GRU Cancer Center Georgia Regents UniversityAugustaGA 30912USA Department of Pediatrics The University of Hong Kong—Shenzhen HospitalShenzhen 518053China

Natural killer (NK) cells are indispensable components of both the innate and adaptive immune response. However,their precise roles in the cross-talk between innate and adaptive immunity during influenza virus infection remaincontroversial. By comparing NK cell dynamics and activity under a sub-lethal dose and high dose of influenza virusinfection, we showed that influenza virus PR8 directly infected NK cells during natural infection, which wasconsistent with our previous findings obtained from an in vitro investigation of human NK cells. The impairments incytotoxicity and IFN-γ production by spleen NK cells following high-dose infection were accompanied by decreasedvirus-specific killing mediated by cytotoxic T lymphocytes (CTLs). Importantly, the weakened CTL activity could bereversed by adoptive transfer of spleen NK cells harvested from low-dose-infected mice but not healthy *** together, our data provide direct evidence supporting the contribution of NK cells to antiviral T-cellresponses. This study also indicates that a novel NK-targeted immune evasion strategy is used by influenza virusto shrink both innate and adaptive immune responses.

关键词： CTL influenza NK cell

Solving the genetic puzzle of systemic lupus erythematosus(SLE)

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Solving the genetic puzzle of systemic lupus erythematosus(S...

Avian influenza virus directly infects human natural killer cells and inhibits cell activity

第九届全国免疫学学术大会

作者： Wanling Yang yu lung lau Department of Paediatrics and Adolescent Medicine The University of Hong Kong

In recent years,genome-wide association studies on systemic lupus erythematosus(SLE)have significantly improved our understanding of the genetic architecture of this prototypic autoimmune ***,there is still a long way to go before we can fully understand the genetics of this very heterogeneous disease,as the susceptibility genes discovered

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Virologica Sinica 2017年第2期32卷 122-129页

作者： Huawei Mao Yinping Liu Sin Fun Sia JS Malik Peiris yu-lung lau Wenwei Tu Department of Paediatrics The University of Hong Kong - Shenzhen Hospital Shenzhen 518000 China Department of Paediatrics & Adolescent Medicine Li Ka Shing Faculty of Medicine The University of Hong Kong Hong Kong SAR China Department of Microbiology The University of Hong Kong Hong Kong SAR China Shenzhen Engineering Laboratory of PID Diagnosis & Therapy Technology Shenzhen 518000 China

Natural killer （NK） cell is a key component of innate immunity and plays an important role in host defense against virus infection by directly destroying infected cells. Influenza is a respiratory disease transmitted in the early phase of virus infection. Evasion of host innate immunity including NK cells is critical for the virus to expand and establish a successful acute infection. Previously, we showed that human influenza HIN1 virus infects NK cells and induces cell apoptosis, as well as inhibits NK cell activity. In this study, we further demonstrated that avian influenza virus also directly targeted NK cells as an immunoevasion strategy. The avian virus infected human NK cells and induced cell apoptosis. In addition, avian influenza virion and HA protein inhibited NK cell cytotoxicity. This novel strategy has obvious advantages for avian influenza virus, allowing the virus sufficient time to expand and subsequent spread before the onset of the specific immune response. Our findings provide an important clue for the immunopathogenesis of avian influenza, and also suggest that direct targeting NK cells may be a common strategy used by both human and avian influenza viruses to evade NK cell immunity.

关键词： natural killer (NK) cell avian influenza virus (AIV) immunoevasion directioninfection inhibition cytotoxicity

Glucose metabolism controls humanγδ-cell-mediated tumor immunosurveillance in diabetes

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Cellular & Molecular Immunology 2022年第8期19卷 944-956页

作者： Xiaofeng Mu Zheng Xiang Yan Xu Jing He Jianwen Lu yuyuan Chen Xiwei Wang Chloe Ran Tu Yanme Wenyue Zhang Zhinan Yin Wing-hang Leung yu-lung lau Yinping Liu Wenwei Tu Department of Pediatrics and Adolescent Medicine Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong SARPR China The First Affliated Hospital Faculty of Medical ScienceJinan UniversityGuangzhou 510632 GuangdongPR China Zhuhai Precision Medical Center Zhuhai People's Hospital(Zhuhai Hospital Affliated with Jinan University)Jinan UniversityZhuhai 519000 GuangdongPR China The Biomedical Translational Research Institute Jinan UniversityGuangzhou 510632 GuangdongPR China GuangDong 999 Brain Hospital Guangzhou CityGuangdong ProvincePR China Department of Endocrinology Guangzhou First People's HospitalSchool of MedicineSouth China University of TechnologyGuangzhou 510180PR China Computational and Systems Biology Interdepartmental Program University of CaliforniaLos AngelesLos AngelesCA 90095USA

Patients with type 2 diabetes mellitus(T2DM)have an increased risk of *** effect of glucose metabolism onγδT cells and their impact on tumor surveillance remain ***,we showed that high glucose induced Warburg effect type of bioenergetic profle in Vy9vδ2 T cells,leading to excessive lactate accumulation,which further inhibited lytic granule secretion by impairing the traffcking of cytolytic machinery to the Vy9vδ2 T-cell-tumor synapse by suppressing AMPK activation and resulted in the loss of antitumor activity in vitro,in vivo and in ***,activating the AMPK pathway through glucose control or metformin treatment reversed the metabolic abnormalities and restored the antitumor activity of Vy9vδ2 T *** results suggest that the impaired antitumor activity of Vy9vδ2 T cells induced by dysregulated glucose metabolism may contribute to the increased cancer risk in T2DM patients and that metabolic reprogramming by targeting the AMPK pathway with metformin may improve tumor immunosurveillance.

关键词： γδT cells Glucose metabolism Tumor surveillance Lactate AMPK T2DM

In-depth cDNA Library Sequencing Provides Quantitative Gene Expression Profiling in Cancer Biomarker Discovery

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Genomics,Proteomics & Bioinformatics 2009年第Z1期 1-12页

作者： Wanling Yang, Dingge Ying, and yu-lung lau Department of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.

关键词： cDNA sequencing sequencing depth expressed sequence tag sequence-specific subtraction biomarker mutation detection