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%r9 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.
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 throug( 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.
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 signaturen 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.
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."
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 Immunity under 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,*,#
1 Institute of Cellular Medicine, Newcastle University, UK
2 Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore
3 Singapore General Hospital, Singapore
4 University of Glasgow Centre for Virus Research, University of Glasgow, UK
5 National University Hospital, Singapore
6 Yong Loo Lin School of Medicine, National University of Singapore
7 KK Women's and Children's Hospital, Singapore
8 Duke-NUS Graduate Medical School, Singapore
9 Singapore 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 or Florent Ginhoux
Institute of Cellular Medicine
Newcastle upon Tyne NE2 4HHUK
Tel: (44) 191 222 7785
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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.
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