Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Natural suppressors of a treatment-induced disease

13.07.2009
A naturally occurring population of dendritic cells reduces the incidence and severity of graft-versus-host-disease in mice

Researchers in Japan have shown that mouse dendritic cells (DCs), which can promote or inhibit inflammation depending on the proteins displayed on their surface, include a subpopulation that exerts beneficial effects during a treatment for leukemia and other malignancies.

The treatment—known as allogeneic hematopoietic stem cell transplantation (alloHSCT)—can, in some situations, result in graft-versus-host-disease (GVHD). Acute and chronic GVHD occur when donor immune cells called T lymphocytes recognize and become activated by proteins present on recipient but not donor tissues. The resulting T lymphocyte-driven immune response can result in severe damage to the recipient skin, gastrointestinal tract and liver.

Previous work by these researchers described the generation of regulatory DCs from mouse bone marrow (BM-DCregs) that, when injected after alloHSCT, reduce the severity and incidence of acute and chronic GVHD. The team, led by Katsuaki Sato at the RIKEN Research Center for Allergy and Immunology in Yokohama, has now shown that naturally occurring counterparts of BM-DCregs exist and influence the outcome of alloHSCT in mice1.

The researchers started by searching for genes associated with immunosuppressive DC function. A comparison of the genes expressed in BM-DCregs and non-regulatory DCs revealed that the gene encoding the surface protein CD200R3 is expressed exclusively in BM-DCregs. They found that blockade of CD200R3 impaired the ability of BM-DCregs to suppress proliferation of T lymphocytes, whereas forced expression of CD200R3 in non-regulatory DCs reduced their ability to promote T lymphocyte cell division. This indicates that CD200R3 contributes to the immunosuppressive function of BM-DCregs.

Reasoning that naturally occurring regulatory DCs might also express CD200R3, the researchers screened blood and spleen cells for CD200R3 expression. They identified a small population of CD200R3-expressing cells that, like BM-DCregs, produced immunosuppressive cytokines, which are regulators of the immune system, and inhibit T cell proliferation. These CD200R3+ DCs exhibited a different morphology than non-regulatory DCs (Fig. 1).

When injected after alloHSCT, Sato and colleagues found that these CD200R3+ DCs—like BM-DCregs—suppressed the onset and severity of GVHD. Recipients of BM-DCregs contained lower amounts of serum proinflammatory proteins, and higher numbers of immunosuppressive regulatory T lymphocytes. Further highlighting the biological importance of BM-DCregs, pre-treatment with a CD200R3-blocking antibody prior to alloHSCT exacerbated GVHD.

“The functional identification of naturally occurring human DCregs, as well as their counterparts generated the laboratory, may provide an advantageous means of intervening to prevent chronic GVHD after alloHSCT” says Sato.

Reference

1. Sato, K., Eizumi, K., Fukaya, T., Fujita, S., Sato, Y., Takagi, H., Yamamoto, M., Yamashita, N., Hijikata, A., Kitamura, H., Ohara, O., Yamasaki, S., Saito, T. & Sato, K. Naturally occurring regulatory dendritic cells regulate murine cutaneous chronic graft-versus-host disease. Blood 113, 4780–4789 (2009).

The corresponding author for this highlight is based at the RIKEN Laboratory for Dendritic Cell Immunobiology

Saeko Okada | Research asia research news
Further information:
http://www.rikenresearch.riken.jp/research/742/

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Supersensitive through quantum entanglement

28.06.2017 | Physics and Astronomy

X-ray photoelectron spectroscopy under real ambient pressure conditions

28.06.2017 | Physics and Astronomy

Mice provide insight into genetics of autism spectrum disorders

28.06.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>