05:04pm Tuesday 17 October 2017

Discovery of immune cell reveals target for better vaccine design

The cell is a type of human tissue dendritic cell and was identified by researchers from Newcastle University in collaboration with A*STAR’s Singapore Immunology Network (SIgN).

Dendritic cells are the sentinels of the immune system, constantly scanning the tissues in the body for signs of anything out of the ordinary. When they are alerted to something unusual, such as the presence of infectious agents like bacteria and viruses or cancer, they kick-start the body’s immune response. They are also very important for eliciting the immune responses generated by vaccines.

To initiate an immune response, dendritic cells take small fragments of molecules called antigens and present them on their surface. This leads to activation of another white blood cell subset called killer T cells, which specialise in killing unusual cells and are crucial for eliminating cancerous or infected cells.

Most cells are only able to present antigens from within themselves and, consequently, will only elicit a killer T-cell immune response if they are infected themselves. Only a specialised subset of dendritic cells is able to generate a response to an external source of antigen, for example bacteria, vaccines and tumours. This process is called ‘cross-presentation’.

Although scientists have known for many years that dendritic cells must be capable of cross-presentation, the exact identity of the cell type responsible has remained a mystery. The discovery of this new dendritic cell subtype, as revealed by this research, will help scientists to design better targeted vaccine strategies to treat cancer and virus infections such as hepatitis B.

“These are the cells we need to be targeting for anti-cancer vaccines,” said Dr Muzlifah Haniffa, a Wellcome Trust Intermediate Fellow and Senior Clinical Lecturer at Newcastle University. “Our discovery offers an accessible, easily targetable system which makes the most of the natural ability of the cell.”

The researchers also showed for the first time that dendritic cell subsets are conserved between species and have created a map to facilitate the translation of mouse studies to the human immune system.

The team isolated dendritic cells from human blood and skin and from mouse blood, lung and liver. Using gene expression analysis, they identified gene signatures for each human dendritic cell subset. The mouse equivalents of these genes were identified and a computational analysis was performed to match subsets across species.

Matthew Collin, Professor of Haematology from Newcastle University, explains: “The cross-species map is, in effect, a Rosetta stone that deciphers the language of mouse into human.”

Dr Haniffa added: “These gene signatures are available in a public repository accessible for all researchers to benefit from the data. It will allow detailed knowledge of individual human dendritic cell subsets to enable specific targeting of these cells for therapeutic strategy.”

The study is published this month in the journal ‘Immunity’.

Image: An immature dendritic cell. Credit: Professor Gareth Jones, Wellcome Images.

Reference

Haniffa M et al. Human tissues contain CD141(hi) cross-presenting dendritic cells with functional homology to mouse CD103(+) nonlymphoid dendritic cells. Immunity 2012.

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