Role of Dendritic Cell Activation in the Pathogenesis of Hepatic Fibrosis

树突状细胞激活在肝纤维化发病机制中的作用

• 批准号: 8673488
• 负责人: George Miller
• 金额: $ 14.86万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-21 至 2016-01-20
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8673488
• 关键词: Accounting; Affect; Antigen-Presenting Cells; Antigens; CCL11 gene; CCL2 gene; CCL22 gene; CCL23 gene; Cell Culture Techniques; Cell physiology; Complex; Dendritic Cells; Dendritic cell activation; Deposition; Development; Dose; Effector Cell; Extracellular Matrix; Fibrosis; Grant; Hepatic; Hepatic Stellate Cell; Immune; Immune Tolerance; Immune response; Immunity; Immunosuppression; In Vitro; Inflammation Mediators; Inflammatory; Injury to Liver; Interleukin-13; Interleukin-4; Interleukin-5; Interleukin-6; Liver; Liver Cirrhosis; Liver Fibrosis; Liver parenchyma; Lymphoid Tissue; Macrophage Inflammatory Protein-1; Mediator of activation protein; Molecular; Mus; Natural Killer Cells; Nodal; Organ; Pathogenesis; Phenotype; Process; Public Health; Role; Solid; Staging; T cell anergy; T-Lymphocyte; TNF gene; Therapeutic; Toxin; Virus; Work; cell type; chemokine; cytokine; cytotoxic; immunogenic; immunogenicity; in vivo; liver function; liver injury; liver transplantation; research study; response

Specific aims of this study are (i) To determine whether liver DC convert from inert inducers of tolerance to potent immune-stimulators and mediators of inflammation in liver fibrosis, (ii) To determine the contributory role of DC in the pathogenesis of fibrosis and their direct role in HSC activation, (iii) To determine whether blockade of the immunogenic function of liver DC can mitigate the fibrogenic response to liver injury. In vitro and in vivo experiments in Aims 2 and 3 were affected by our loss of cell cultures, mice, and our lab shutdown and then relocation. An extension will help us complete the Aims of the grant which has been very fruitful till this point.

本研究的具体目的是（i）确定肝DC是否从惰性诱导剂转化， 对肝纤维化中的强效免疫刺激剂和炎症介质的耐受性，（ii） 确定DC在纤维化发病机制中的贡献作用及其在HSC中的直接作用 （iii）为了确定阻断肝DC的免疫原性功能是否可以 减轻对肝损伤的纤维化反应。目标2和3的体外和体内实验 受到了细胞培养物和小鼠的损失，以及实验室关闭和搬迁的影响。一个 延期将帮助我们完成赠款的目标，到目前为止，赠款已经取得了丰硕的成果。

项目成果

Interleukin 17-producing γδT cells promote hepatic regeneration in mice.

产生白细胞介素 17 的 γδT 细胞促进小鼠肝脏再生。

• DOI: 10.1053/j.gastro.2014.04.042
• 发表时间: 2014-08
• 期刊: Gastroenterology
• 影响因子: 29.4
• 作者: Rao R;Graffeo CS;Gulati R;Jamal M;Narayan S;Zambirinis CP;Barilla R;Deutsch M;Greco SH;Ochi A;Tomkötter L;Blobstein R;Avanzi A;Tippens DM;Gelbstein Y;Van Heerden E;Miller G
• 通讯作者: Miller G

RIP1 Kinase Drives Macrophage-Mediated Adaptive Immune Tolerance in Pancreatic Cancer.

• DOI: 10.1016/j.ccell.2018.10.006
• 发表时间: 2018-11-12
• 期刊: Cancer cell
• 影响因子: 50.3
• 作者: Wang W;Marinis JM;Beal AM;Savadkar S;Wu Y;Khan M;Taunk PS;Wu N;Su W;Wu J;Ahsan A;Kurz E;Chen T;Yaboh I;Li F;Gutierrez J;Diskin B;Hundeyin M;Reilly M;Lich JD;Harris PA;Mahajan MK;Thorpe JH;Nassau P;Mosley JE;Leinwand J;Kochen Rossi JA;Mishra A;Aykut B;Glacken M;Ochi A;Verma N;Kim JI;Vasudevaraja V;Adeegbe D;Almonte C;Bagdatlioglu E;Cohen DJ;Wong KK;Bertin J;Miller G
• 通讯作者: Miller G