Researchers in Newcastle and Singapore have identified a new type of
white blood cell which activates a killing immune response to an external
source – providing a new potential target for vaccines for conditions such as
cancer or Hepatitis B.
Publishing in the journal
Immunity, the team of researchers from Newcastle University in collaboration
with A*STAR's Singapore Immunology Network (SIgN) describe a new human tissue
dendritic cell with cross-presenting function.
Dendritic cells (DCs) are a type
of white blood cell that orchestrate our body's immune responses to infectious
agents such as bacteria and viruses, as well as cancer cells. They are also
very important for eliciting the immune response generated by vaccines.
DCs kick start an immune response
by presenting small fragments of molecules from micro-organisms such as
bacteria and viruses, or from vaccines or tumours, called antigens on their
surface. This leads to activation of another white blood cell subset called T
cells, which specialise in killing cells and are crucial for eliminating
cancerous or infected cells. Most cells are only able to present antigens from
within themselves, and so will only elicit an immune response if they are
infected themselves. Only a specialised subset of DCs is able to generate a
response to an external source of antigen, for example bacteria, vaccines and
tumours.
The identity of human tissue DCs
that are capable of presenting external antigen to activate the cell-killing
response by T cells - a process termed 'cross-presentation' - has remained a
mystery. Their discovery, as revealed by this research, will help scientists to
design better targeted vaccine strategies to treat cancer and 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 in effect created a map, facilitating the translation of mouse studies to
the human immune system.
"The cross-species map is in
effect a Rosetta stone that deciphers the language of mouse into human",
explains Matthew Collin, Professor of Haematology from Newcastle University.
In the paper the researchers
describe how the cross-presenting DCs were first isolated from surplus plastic
surgery skin which was digested to melt the gelatinous collagen to isolate the
cells.
This research will have
significant impact on the design of vaccines and other targeted
immunotherapies.
The Rosetta Stone of our immune system: Mapping Human and Mouse
dendritic cells
The Newcastle University team in
collaboration with A*STAR's Singapore Immunology Network (SIgN) have for the
first time ever aligned the dendritic cell subsets between mouse and humans
allowing the accurate translation of mouse studies into the human model for the
first time.
The researchers isolated the
dendritic cells from human blood and skin and those from mouse blood, lung and
liver. Using gene expression analysis, they identified gene signatures for each
human dendritic cell subset. Mouse orthologues of these genes were identified
and a computational analysis was performed to match subsets across species.
This provides scientists for the
first time with an accurate model to compare DCs between species.
Professor Matthew Collin
explains: "This is in effect a Rosetta stone that deciphers the language
of mouse into human. It can put into context the findings from the extensive
literature using mouse models to the human settings".
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."
More information: Human Tissues
Contain CD141(hi) Cross-Presenting Dendritic Cells with Functional Homology to
Mouse CD103(+) Nonlymphoid Dendritic Cells. Haniffa M, Shin A, Bigley V,
McGovern N, Teo P, See P, Wasan PS, Wang XN, Malinarich F, Malleret B, Larbi A,
Tan P, Zhao H, Poidinger M, Pagan S, Cookson S, Dickinson R, Dimmick I, Jarrett
RF, Renia L, Tam J, Song C, Connolly J, Chan JK, Gehring A, Bertoletti A,
Collin M, Ginhoux F. Immunity. 2012.
Provided
by Newcastle
University
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