Scientists from Singapore Immunological Network Discover Dendritic Cells Key to

StephenW

Press Releases                                                                                        

Monday, July 16, 2012

Scientists from Singapore Immunological Network Discover Dendritic Cells Key to Activating Human Immune Responses                                                                                                                                                                           1.         Scientists at A*STAR’s Singapore Immunology Network (SIgN), in collaboration with Newcastle University, UK, the Singapore Institute of Clinical Sciences and clinicians from multiple hospitals in Singapore, have identified a new subset of dendritic cells (DCs) in human peripheral tissue which have a critical role in activating our immune response against harmful pathogens. This research will have significant impact on the design of vaccines and other targeted immunotherapies. The scientists also showed for the first time that DC subsets are conserved between species, facilitating the translation of mouse functional DC studies to the human setting. These research findings were published in the July issue of the prestigious journal Immunity. 2.         All immune responses against harmful pathogens are activated and regulated by DCs, which present antigens (protein components from micro-organisms, vaccines or tumours) to the T cells. Of the different T cells, the cytotoxic CD8+ T cells specialize in cell-killing response and are crucial for our body to eliminate cancer or infected cells. However, only a small subset of DCs is capable of presenting externally derived antigens to activate this cell-killing response through a process termed “cross-presentation”. The identity of this subset of DCs in human tissue has been a mystery but the SIgN scientists and collaborators have now identified the human cross-presenting DC subset. This discovery enables better exploitation of targeted vaccine strategies to treat cancer and infection. 3.         In this paper, Dr Florent Ginhoux, Principal Investigator at SIgN and his collaborators, identified in human tissues, including dermis, lung and liver, a new subset of DCs, called CD141hi DC and described its genetic signature. They also showed for the first time that CD141hi DCs were superior at cross-presenting soluble antigens compared to other DCs to activate the killer T cells. The scientists also carried out a comparison of human and mouse DC subsets and demonstrated that there was close alignment of the DC subsets between species. Functional alignment of human and mouse DC subsets had previously been hampered by differences in surface marker expression and accessibility of equivalent sources. This detailed study now aligns the mouse and human DC networks, and will facilitate better translation of mouse DC studies to the human setting. 4.         Dr Ginhoux, said, “This was technically very challenging work as we only had limited quantities of human tissue samples and limited amount of cells to work with. But we managed to obtain the full gene expression profile of tissue DC, including for this new CD141hi DC subset. This knowledge will be fundamentally important in learning how to manipulate immune responses to tumors, viruses and vaccines. Importantly, we were very fortunate to have an incredible bioinformatics team in SIgN to perform the intra and interspecies analysis of DCs from human and mouse samples. Our findings will allow scientists to draw clear inferences between mouse and human DC biology.” 5. Scientific Director of SIgN, Professor Paola Castagnoli said, “These findings will facilitate translation of basic research into clinical applications such as future rational vaccine design and targeted immunotherapies. This is a fine example of how scientists and clinicians collaborate to carry out impactful research and benefit people.” Notes for editor: The research findings described in this media release can be found in the 12 July online issue of Immunityunder the title, "Human tissues contain CD141hi dendritic cells with cross-presenting capacity and functional homology to mouse CD103+ non-lymphoid dendritic cells” by Muzlifah Haniffa1,2, Amanda Shin2,*, Venetia Bigley 1,*, Naomi McGovern1, Pearline Teo2, Peter See2, Pavandip Singh Wasan2, Xiao-Nong Wang1, Frano Malinarich2, Benoit Malleret2, Anis Larbi2, Pearlie Tan3, Helen Zhao2, Michael Poidinger2, Sarah Pagan1, Sharon Cookson1, Rachel Dickinson1, Ian Dimmick1, Ruth F. Jarrett4, Laurent Renia2, John Tam5,6, Colin Song3, John Connolly2, Jerry K.Y. Chan6,7,8, Adam Gehring9, Antonio Bertoletti9, Matthew Collin1,*,# and Florent Ginhoux2,*,# 1Institute of Cellular Medicine, Newcastle University, UK 2Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore 3Singapore General Hospital, Singapore 4 University of Glasgow Centre for Virus Research, University of Glasgow, UK 5National University Hospital, Singapore 6Yong Loo Lin School of Medicine, National University of Singapore 7 KK Women’s and Children’s Hospital, Singapore 8Duke-NUS Graduate Medical School, Singapore 9Singapore Institute of Clinical Sciences, Agency for Science, Technology and Research (A*STAR), Singapore *Equal contribution with adjacent author #Correspondence should be addressed to: Matthew Collin ([email protected]) or Florent Ginhoux ([email protected]) Matthew Collin Institute of Cellular Medicine Newcastle University Framlington Place Newcastle upon Tyne NE2 4HHUK Tel: (44) 191 222 7785 Email: [email protected] Florent Ginhoux, Singapore Immunology Network (SIgN) Agency for Science, Technology and Research (A*STAR) 8A Biomedical Grove, IMMUNOS Building #3-4 BIOPOLIS, 138648, Singapore. Tel: (65) 64070410 Email: [email protected]   AGENCY FOR SCIENCE, TECHNOLOGY AND RESEARCH (A*STAR) For media queries and clarifications, please contact: Ong Siok Ming (Ms) Senior Officer, Corporate Communications Agency for Science, Technology and Research Tel: (+65) 6826 6254 Email: [url=mailto[email protected]][email protected][/url] About the Singapore Immunology Network (SIgN) The Singapore Immunology Network (SIgN), officially inaugurated on 15 January 2008, is a research consortium under the Agency for Science, Technology and Research (A*STAR)’s Biomedical Research Council. The mandate of SIgN is to advance human immunology research and participate in international efforts to combat major health problems. Since its launch, SIgN has grown rapidly and currently includes 200 scientists from 25 different countries around the world working under 20 renowned principal investigators. At SIgN, researchers investigate immunity during infection and various inflammatory conditions including cancer and are supported by cutting edge technological research platforms and core services. Through this, SIgN aims to build a strong platform in basic human immunology research for better translation of research findings into clinical applications. SIgN also sets out to establish productive links with local and international institutions, and encourage the exchange of ideas and expertise between academic, industrial and clinical partners and thus contribute to a vibrant research environment in Singapore. For more information about SIgN, please visit www.sign.a-star.edu.sg. About the Agency for Science, Technology and Research (A*STAR) The Agency for Science, Technology and Research (A*STAR) is the lead agency for fostering world-class scientific research and talent for a vibrant knowledge-based and innovation-driven Singapore. A*STAR oversees 14 biomedical sciences and physical sciences and engineering research institutes, and six consortia & centres, located in Biopolis and Fusionopolis as well as their immediate vicinity. A*STAR supports Singapore's key economic clusters by providing intellectual, human and industrial capital to its partners in industry. It also supports extramural research in the universities, and with other local and international partners. For more information about A*STAR, please visit www.a-star.edu.sg.

StephenW

新闻公报

2012年7月16日，星期一，
来自新加坡的免疫网络的科学家发现树突状细胞激活人体的免疫应答的关键

1。 A * STAR的新加坡免疫学网络（SIGN）在与纽卡斯尔大学，英国，新加坡临床科学和新加坡多个医院临床学院合作，，科学家已经确定人类的外围组织1树突状细胞的新的子集（DC）的这在激活我们的免疫反应，防止有害病原体有至关重要的作用。这项研究将有疫苗和其他有针对性的免疫疗法的设计上显着的影响。科学家们还发现，物种间保守的DC亚群为首次，促进人类设置鼠标功能的直流研究翻译。这些研究结果发表在权威杂志的免疫力七月问题。

2。所有防止有害病原体的免疫反应被激活，并受区议会，而目前的抗原（蛋白质成分的微生物，疫苗或肿瘤）T细胞。不同的T细胞，细胞毒性CD8 + T细胞专注于细胞的杀伤反应，是我们的身体，以消除癌症或感染细胞的关键。然而，只有一小部分区议会是能够呈现外部派生抗原的激活通过一个过程被称为“交叉呈现”这种细胞的杀伤反应。本区议会在人体组织中的一个子集的身份一直是个谜，但标志科学家和合作者已经确定人类的交叉呈现DC亚群。这一发现可以更好地开发有针对性的疫苗策略来治疗癌症和感染。

3。在本文，弗洛伦特Ginhoux博士，首席研究员和他的合作者at符号，确定了在人体组织中，包括真皮，肺和肝，区议会的一个新的子集，称为CD141hi直流，并阐述了其遗传特征。他们还发现，CD141hi议会优越激活杀伤性T细胞相比其他区议会交呈可溶性抗原的首次。科学家们还进行了人类和小鼠的DC亚群的比较表明，有DC亚群的物种之间的密切协调。人类和小鼠的DC亚群功能对准以前一直阻碍了在等效源表面标志的表达和无障碍的差异。现在这方面的详细研究赞同老鼠和人类的直流网络，将有利于更好的鼠标直流研究人类设置的翻译。

4。博士Ginhoux说，“这在技术上是非常具有挑战性的工作，因为我们只有人体组织样本和细胞的数量有限数量有限的工作。但我们设法获得组织直流全基因的表达谱，包括这个新CD141hi DC亚群。在学习如何控制肿瘤​​，病毒和疫苗的免疫反应，这方面的知识将是极其重要的。重要的是，我们很幸运，有一个令人难以置信的生物信息学团队，登录执行的内部和种间议会从人类和小鼠的样品分析。我们的发现将帮助科学家利用老鼠和人类的直流生物学之间的明确推论。“

5。 Castagnoli酒店保拉教授说，标志的科学主任，“这些发现将有助于翻译到如未来合理的疫苗设计和有针对性的免疫疗法的临床应用基础研究。科学家和临床医生如何合作开展有影响力的研究，造福人类，这是一个很好的例子。“

为编辑的注意事项：

在研究本新闻稿中所描述的结果可以得到的12 7月的标题下免疫功能的网上发行中发现，“人体组织包含与交叉，呈现能力和功能的同源性小鼠CD103 +非淋巴树突状细胞CD141hi树突状细胞”由Muzlifah Haniffa1 ，阿曼达Shin2，2，*，威尼斯比格利1，*，拿俄米McGovern1，Pearline碲，彼得SEE2，Pavandip辛格Wasan2，晓农Wang1，Frano Malinarich2，Malleret2伯努瓦，Larbi2阿尼斯，Pearlie Tan3，海伦Zhao2，迈克尔Poidinger2萨拉Pagan1莎朗Cookson1，雷切尔Dickinson1，伊恩Dimmick1，露丝楼Jarrett4，洛朗Renia2，6约翰Tam5，科林Song3约翰Connolly2，杰里肯塔基Chan6，安东尼奥·亚当Gehring9 Bertoletti9，马修Collin1，*，7,8，， ＃和弗洛伦特Ginhoux2，*，＃


1细胞医学，英国纽卡斯尔大学

2Singapore免疫网络，为科学，技术和研究局（A * STAR），新加坡

新加坡3Singapore总医院，

4格拉斯哥病毒研究中心，大学，英国格拉斯哥大学

5National大学医院，新加坡

6Yong潞龄医学院，新加坡国立大学

7株式会社妇女和儿童医院，新加坡

8Duke新加坡国立大学医学院研究生学院，新加坡

9Singapore，科学，技术和研究局（A * STAR），新加坡临床科学研究所

*相邻作者同等贡献

＃函授教育应寄往：马修·科林

（matthew.collin @ newcastle.ac.uk）或尼古拉Ginhoux的
（[email protected]）


马修·科林
细胞医学研究所
纽卡斯尔大学
framlington广场
纽卡斯尔泰恩NE2 4HHUK
电话：（44）191 222 7785
电子邮件：matthew.collin @ newcastle.ac.uk

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