检索结果-南通市图书馆

Treatment with a JAK1/2 inhibitor ameliorates murine autoimmune cholangitis induced by IFN overexpression

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Cellular & Molecular Immunology 2022年第10期19卷 1130-1140页

作者： Tihong Shao Patrick S.C.Leung weici zhang Koichi Tsuneyama William M.Ridgway Howard A.Young Zongwen Shuai Aftab A.Ansari M.Eric Gershwi Department of Rheumatology and Immunology The First Affiliated Hospital of Anhui Medical UniversityHefeiChina Division of Rheumatology Allergyand Clinical ImmunologySchool of MedicineUniversity of CaliforniaDavisCAUSA Department of Pathology and Laboratory Medicine Institute of Biomedical SciencesTokushima University Graduate SchoolTokushimaJapan Center for Cancer Research National Cancer Institute-FrederickFrederickMDUSA

The interferon(IFN)signaling pathways are major immunological checkpoints with clinical significance in the pathogenesis of autoimmunity.We have generated a unique murine model named ARE-Del,with chronic overexpression of IFNγ,by altering IFNγmetabolism.Importantly,these mice develop an immunologic and clinical profile similar to patients with primary biliary cholangitis,including high titers of autoantibodies and portal inflammation.We hypothesized that the downregulation of IFN signaling pathways with a JAK1/2 inhibitor would inhibit the development and progression of cholangitis.To study this hypothesis,ARE-Del^(+/−)mice were treated with the JAK1/2 inhibitor ruxolitinib and serially studied.JAK inhibition resulted in a significant reduction in portal inflammation and bile duct damage,associated with a significant reduction in splenic and hepatic CD4^(+)T cells and CD8^(+)T cells.Functionally,ruxolitinib inhibited the secretion of the proinflammatory cytokines IFNγand TNF from splenic CD4^(+)T cells.Additionally,ruxolitinib treatment also decreased the frequencies of germinal center B(GC B)cells and T follicular helper(Tfh)cells and led to lower serological AMA levels.Of note,liver and peritoneal macrophages were sharply decreased and polarized from M1 to M2 with a higher level of IRF4 expression after ruxolitinib treatment.Mechanistically,ruxolitinib inhibited the secretion of IL-6,TNF and MCP1 and the expression of STAT1 but promoted the expression of STAT6 in macrophages in vitro,indicating that M1 macrophage polarization to M2 occurred through activation of the STAT6-IRF4 pathway.Our data highlight the significance,both immunologically and clinically,of the JAK/STAT signaling pathway in autoimmune cholangitis.

关键词： Primary biliary cholangitis Autoimmunity Interferons Janus Kinase Inhibitors Ruxolitinib

Long noncoding RNA lncKdm2b: A critical player in the maintenance of group 3 innate lymphoid cells

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Cellular & Molecular Immunology 2018年第1期15卷 5-7页

作者： Can-Jie Guo weici zhang M Eric Gershwin Division of Gastroenterology and Hepatology Key Laboratory of Gastroenterology and HepatologyMinistry of HealthRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai Institute of Digestive Disease Shanghai Institute of Digestive Disease Shanghai200001China Division of Rheumatology Allergy and Clinical ImmunologySchool of MedicineUniversity of CaliforniaDavis95616CAUSA

Innate lymphoid cells(ILCs)represent a heterogeneous population,including both effectors and regulators of innate immunity,inflammation and tissue modeling.1 ILCs are categorized into three subgroups,ILC1s,ILC2s and ILC3s,based on similarities in phenotypic,ontogenetic and functional characteristics.2 ILC3s intrinsically require the transcription factor retinoic acid receptor-related orphan receptorγt(RORγt)for their development and function.3 In response to specific stimuli,ILC3s produce IL-17 and IL-22 and play a critical role in intestinal mucosal protection,inflammation and innate responses 4 accompanied by a series of pathophysiological changes involving large-scale genetic upregulation and downregulation.5,6 However,a key challenge remains in understanding the molecular mechanisms underlying the development and maintenance of ILC3s.

关键词： lymphoid inflammation immunity

Exosomal microRNA in autoimmunity

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Cellular & Molecular Immunology 2019年第12期16卷 932-934页

作者： Weijia Duan weici zhang Jidong Jia Qianjin Lu M.Eric Gershwin Beijing Key Laboratory of Translational Medicine on Cirrhosis Liver Research CenterNational Clinical Research Center for Digestive DiseasesBeijing Friendship HospitalCapital Medical University100050 BeijingChina Division of Rheumatology Allergy and Clinical ImmunologyUniversity of CaliforniaDavisCA 95616USA Department of Dermatology Second Xiangya HospitalHunan Key Laboratory of Medical EpigenomicsCentral South UniversityChangsha 410011 HunanChina

Exosomes are small extracellular vesicles that contain a potpourri of nucleic acids,including microRNAs(miRNAs).Importantly,exosomes and these miRNAs are actively secreted from multiple cell populations and play a critical role in intercellular communication.The exosomal miRNA profile reflects the cellular pathophysiological status and modulates multiple biological processes.Accumulating evidence indicates that exosomes and miRNAs are biomarkers for disease diagnosis and may have therapeutic targets.Research studies on exosomal miRNAs have brought new insights into understanding autoimmune diseases.This article summarizes the detection methodologies and updates the potential applications of exosomal miRNAs in autoimmune diseases.

关键词： somal diagnosis autoimmune

BCTCP:A Feedback-Based Congestion Control Method

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

China Communications 2020年第6期17卷 13-25页

作者： Yuyu Zhao Guang Cheng weici zhang Xin Chen Jin Li School of Cyber Science&Engineering Southeast UniversityNanjing 211189China Key Laboratory of Computer Network and Information Integration of Ministry of Education Southeast UniversityNanjing 211189China Key Laboratory of Computer Network Technology of Jiangsu Province China Huawei Technologies Co. Ltd.No 101Software AvenueNanjing 211189China

Delay and throughput are the two network indicators that users most care about.Traditional congestion control methods try to occupy buffer aggressively until packet loss being detected,causing high delay and variation.Using AQM and ECN can highly reduce packet drop rate and delay,however they may also lead to low utilization.Managing queue size of routers properly means a lot to congestion control method.Keeping traffic size varying around bottleneck bandwidth creates some degree of persistent queue in the router,which brings in additional delay into network unwillingly,but a corporation between sender and router can keep it under control.Proper persistent queue not only keeps routers being fully utilized all the time,but also lower the variation of throughput and delay,achieving the balance between delay and utilization.In this paper,we present BCTCP(Buffer Controllable TCP),a congestion control protocol based on explicit feedback from routers.It requires sender,receiver and routers cooperating with each other,in which senders adjust their sending rate according to the multiple bit load factor information from routers.It keeps queue length of bottleneck under control,leading to very good delay and utilization result,making it more applicable to complex network environments.

关键词： explicit congestion control active queue management delay variation low latency high throughput

Proteomic analysis reveals distinctive protein profiles involved in CD8^(+) T cell-mediated murine autoimmune cholangitis

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Cellular & Molecular Immunology 2018年第8期15卷 756-767页

作者： weici zhang Ren zhang Jun zhang Ying Sun Patrick SC Leung Guo-Xiang Yang Zongwen Shuai William M Ridgway M Eric Gershwin Division of Rheumatology Allergy and Clinical ImmunologyUniversity of CaliforniaDavisCaliforniaUSA Department of Pathogenic Biology and Immunology Guangzhou University of Chinese MedicineGuangzhou 510006China Center for non-infectious liver diseases Beijing 302 HospitalBeijing 100039China Department of Rheumatology and Immunology The First Affiliated Hospital of Anhui Medical UniversityHefei 230022China Division of Immunology Allergy and RheumatologyUniversity of CincinnatiCincinnatiOH 45267

Autoimmune cholangitis arises from abnormal innate and adaptive immune responses in the liver,and T cells are critical drivers in this process.However,little is known about the regulation of their functional behavior during disease development.We previously reported that mice with T cell-restricted expression of a dominant negative form of transforming growth factor beta receptor type Ⅱ(dnTGFβ RII)spontaneously develop an autoimmune cholangitis that resembles human primary biliary cholangitis(PBC).Adoptive transfer of CD8^(+) but not CD4^(+) T cells into Rag1^(−/−)mice reproduced the disease,demonstrating a critical role for CD8^(+) T cells in PBC pathogenesis.Herein,we used SOMAscan technology to perform proteomic analysis of serum samples from dnTGFβRII and B6 control mice at different ages.In addition,we analyzed CD8 protein profiles after adoptive transfer of splenic CD8^(+) cells into Rag1^(−/−)recipients.The use of the unique SOMAscan aptamer technology revealed critical and distinct profiles of CD8 cells,which are key to biliary mediation.In total,254 proteins were significantly increased while 216 proteins were significantly decreased in recipient hepatic CD8^(+) cells compared to donor splenic CD8^(+) cells.In contrast to donor splenic CD8^(+) cells,recipient hepatic CD8^(+) cells expressed distinct profiles for proteins involved in chemokine signaling,focal adhesion,T cell receptor and natural killer cell-mediated cytotoxicity pathways.

关键词： autoimmune cholangitis CD8 dnTGFβRII mice proteomic analysis

Adaptive immunity in the liver

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Cellular & Molecular Immunology 2016年第3期13卷 354-368页

作者： Zongwen Shuai Miranda WY Leung Xiaosong He weici zhang Guoxiang Yang Patrick SC Leung M Eric Gershwin Division of Rheumatology Allergy and Clinical Immunology University of California Davis School of Medicine Davis CA 95616 USA Department of Rheumatology and Immunology The First Affiliated Hospital of Anhui Medical University Hefei 230022 China.

The anatomical architecture of the human liver and the diversity of its immune components endow the liver with its physiological function of immune competence. Adaptive immunity is a major arm of the immune system that is organized in a highly specialized and systematic manner, thus providing long-lasting protection with immunological memory. Adaptive immunity consists of humoral immunity and cellular immunity. Cellular immunity is known to have a crucial role in controlling infection, cancer and autoimmune disorders in the liver. In this article, we will focus on hepatic virus infections, hepatocellular carcinoma and autoimmune disorders as examples to illustrate the current understanding of the contribution of T cells to cellular immunity in these maladies. Cellular immune suppression is primarily responsible for chronic viral infections and cancer. However, an uncontrolled auto-reactive immune response accounts for autoimmunity. Consequently, these immune abnormalities are ascribed to the quantitative and functional changes in adaptive immune cells and their subsets, innate immunocytes, chemokines, cytokines and various surface receptors on immune cells. A greater understanding of the complex orchestration of the hepatic adaptive immune regulators during homeostasis and immune competence are much needed to identify relevant targets for clinical intervention to treat immunological disorders in the liver.

关键词： adaptive immunity T cells immunopathogenesis antiviral immunity

重庆市土地利用冲突多尺度时空演化与多情景演化模拟

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

生态学报 2024年第3期44卷 1024-1039页

作者：王朝阳张军以李海懿苏维词重庆师范大学地理与旅游学院重庆401331 三峡库区地表过程与环境遥感重庆市重点实验室重庆401331 贵州省山地资源研究所贵阳550001

土地利用冲突是区域土地开发利用过程中存在的客观问题,对区域经济社会发展和生态安全具有重要影响。识别、测度区域土地利用冲突,明晰其时空演化格局,有助于优化区域土地利用结构,促进土地资源的可持续利用。以重庆市为例,基于景观格... 详细信息

土地利用冲突是区域土地开发利用过程中存在的客观问题,对区域经济社会发展和生态安全具有重要影响。识别、测度区域土地利用冲突,明晰其时空演化格局,有助于优化区域土地利用结构,促进土地资源的可持续利用。以重庆市为例,基于景观格局构建了土地利用冲突测度模型,从县域、镇域以及格网3个尺度全面和系统地分析了1995—2020年重庆市土地利用冲突的时空演化特征,并耦合多目标规划(Multi-Objective Programming,MOP)-斑块生成土地利用变化模拟模型(Ptach-generating Land Use Simulation,PLUS)模拟了重庆市2030年不同发展情景下土地利用冲突格局。结果表明:(1)1995—2020年重庆市县域、镇域与格网不同尺度下的土地利用冲突格局具有较大相似性,不同尺度的土地利用重度冲突区主要分布在重庆中心城区及周边地区,区县建成区。土地利用一般冲突区主要分布于渝东南和渝东北地区。研究期内土地利用冲突有所加剧,其中土地利用重度冲突区占比增加了3.09%。(2)1995—2005年重庆市土地利用冲突区主体位于乡村地域,但冲突程度较低,随着工业化、城市化进程及人口的集聚,2005年后土地利用冲突热点区域的城市地域集聚效应显著,城市及周边地区土地利用冲突区面积和土地利用冲突度均显著提升。(3)区域土地利用冲突空间格局不仅受到了人为经济社会活动的驱动影响,在空间格局上受自然生态环境基底影响显著,其中地形地貌的限制加剧了土地利用重度冲突区。(4)不同发展情景模拟中经济优先发展情景下土地利用冲突最为严重,生态优先发展情景下土地利用冲突最小,可持续发展情景兼顾了经济和生态发展的用地需求,土地利用冲突强度处于中间范围,但区域发展总福利最大,是未来区域发展路径最优选择。

关键词：土地利用土地利用冲突多目标规划 PLUS模型多情景模拟重庆市

The modulation of co-stimulatory molecules by circulating exosomes in primary biliary cirrhosis

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Cellular & Molecular Immunology 2017年第3期14卷 276-284页

作者： Takashi Tomiyama Guo-Xiang Yang Ming Zhao weici zhang Hajime Tanaka Jing Wang Patrick SC Leung Kazuiclli Okazaki Xiao-Song He Qianjin Lu Ross L Coppel Christopher L Bowlus M Eric Gershwin Division of Rheumatology Allergy and Clinical Immunology University of California at Davis Davis CA 95616 USA Third Department of Internal Medicine Division of Gastroenterology and Hepatology Kansai Medical University Osaka 573-1191 Japan Hunan Key Laboratory of Medical Epigenomics Department of Dermatology The Second Xiangya Hospital Central South University Changsha Hunan 410011 People's Republic of China Department of Gastroenterology and Metabolism Nagoya City University Graduate School of Medical Sciences Nagoya 467-8601 Japan Department of Microbiology Monash University Melbourne Australia Division of Gastroenterology and Hepatology University of California at Davis School of Medicine. Sacramento. CA 95817. USA

Exosomes are nanoparticles of endocytic origin, secreted by a myriad of cell populations that are attracting increased attention by virtue of their ability to modulate cell-to-cell communications. They are also attracting attention in a variety of immunological issues, including autoimmunity and, in particular, their ability to regulate cytokine and chemokine activation. Primary biliary cirrhosis （PBC） is considered a model autoimmune disease, which has a highly focused cytotoxic response against biliary epithelial cells. We have isolated exosomes from plasma from 29 patients with PBC and 30 healthy controls （HCs）, and studied the effect of these exosomes on co-stimulatory molecule expression and cytokine production in mononuclear cell populations using an ex vivo system. We also identified the microRNA （miRNA） populations in PBC compared to HC exosomes. We report herein that although exosomes do not change cytokine production, they do significantly alter co-stimulatory molecule expression on antigen-presenting populations. Further, we demonstrated that CD86 up-regulated expression on CD14＋ monocytes, whereas CD40 up-regulated on CD11c＋ dendritic cells by exosomes from patients with PBC. In addition, there were differences of miRNA expression of circulating exosomes in patients with PBC. These data have significant importance based on observations that co-stimulatory molecules play a differential role in the regulation of T-cell activation. Our observation indicated that aberrant exosomes from PBC selectively induce expression of co-stimulatory molecules in different subset of antigen-presenting cells. These alterations may involve in pathogenesis of autoimmune liver disease.

关键词： autoimmunity exosome microRNA primary biliary cirrhosis

Liver-resident NK cells suppress autoimmune cholangitis and limit the proliferation of CD4^(+) T cells

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Cellular & Molecular Immunology 2020年第2期17卷 178-189页

作者： Zhi-Bin Zhao Fang-Ting Lu Hong-Di Ma Yin-Hu Wang Wei Yang Jie Long Qi Miao weici zhang Zhigang Tian William M.Ridgway Jie Cao M.Eric Gershwin Zhe-Xiong Lian Department of General Surgery Guangzhou Digestive Disease CenterGuangzhou First People’s HospitalSchool of MedicineSouth China University of TechnologyGuangzhouGuangdong 510180China Chronic Disease Laboratory Institutes for Life Sciences and School of MedicineSouth China University of TechnologyGuangzhou 510006China Institute of Immunology and School of Life Sciences University of Science and Technology of ChinaHefeiAnhui 230027China Center for Reproductive Medicine Anhui Provincial Hospital Affiliated to Anhui Medical UniversityHefeiAnhuiChina Department of Gastroenterology and Hepatology Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Division of Rheumatology Allergy and Clinical ImmunologyUniversity of California at Davis School of MedicineDavisCAUSA Division of Immunology Allergy and RheumatologyUniversity of CincinnatiCincinnatiOH 45267USA

Liver-resident NK cells are distinct from conventional NK cells and play an important role in the maintenance of liver homeostasis.How liver-resident NK cells participate in autoimmune cholangitis remains unclear.Here,we extensively investigated the impact of NK cells in the pathogenesis of autoimmune cholangitis utilizing the well-established dnTGFβRII cholangitis model,NK cell-deficient(Nfil3−/−)mice,adoptive transfer and in vivo antibody-mediated NK cell depletion.Our data demonstrated that disease progression was associated with a significantly reduced frequency of hepatic NK cells.Depletion of NK cells resulted in exacerbated autoimmune cholangitis in dnTGFβRII mice.We further confirmed that the DX5−CD11c^(hi) liver-resident NK cell subset colocalized with CD4^(+) T cells and inhibited CD4^(+) T cell proliferation.Gene expression microarray analysis demonstrated that liver-resident NK cells had a distinct gene expression pattern consisting of the increased expression of genes involved in negative regulatory functions in the context of the inflammatory microenvironment.

关键词： Liver-resident NK Cholangitis CD4^(+)T cell Suppression