Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Holding back immunity

06.02.2012
A ‘gatekeeper’ protein plays a critical role in helping immune cells to sound a warning after encountering signs of tumor growth or infection

When the body’s own cells turn into ticking time bombs, as in cases of viral infection or cancerous transformation, a mechanism known as ‘cross-presentation’ enables the immune system’s dendritic cells (DCs) to sound the alarm.


Figure 1: Compared to untreated dendritic cells (top), cells treated with an HSP90 inhibitor (radicicol) (bottom) tend to retain a larger percentage of the antigen ovalbumin (red; left) within membrane bound endosomes (green; middle). Endosomes are labeled with a stain that marks the membrane protein PKH67. Copyright : 2012 the National Academy of Sciences

“Dendritic cells first internalize cancerous or virus-infected cells through a mechanism called phagocytosis, and then process cellular antigens into short peptides,” explains Heiichiro Udono of the RIKEN Center for Allergy and Immunology in Yokohama. DCs subsequently present these fragments to killer T cells, which seek out and destroy other affected cells. Phagocytosed molecules travel within sealed membrane bubbles called endosomes, and new work from Udono and his colleagues has revealed insights into how these antigens are released into the cytosol prior to cross-presentation1.

Udono’s team focused on heat-shock protein 90 (HSP90), a molecule that previous studies have linked to cross-presentation. HSP90 comes in two forms, á and â, which perform overlapping roles. Mice need at least one of these proteins to live. Udono and colleagues succeeded in generating healthy mice that exclusively lack HSP90á. They found that, although HSP90â appears to make some contribution, the loss of HSP90á had a striking effect on antigen processing. DCs isolated from these mice showed defects in their capacity for cross-presentation, and failed to activate killer T cells efficiently following exposure to ovalbumin, a model antigen.

HSP90á-deficient DCs proved perfectly capable of internalizing ovalbumin within endosomes; however, they generally failed to release this antigen into the cytosol. The researchers noted a similar effect after treating genetically normal DCs with a chemical that inhibits HSP90á (Fig. 1), confirming the central role of this protein in endosomal release.

Udono and colleagues further demonstrated the extent of these defects by injecting HSP90á-deficient mice with cytochrome c, a protein that selectively eliminates a subpopulation of DCs after being taken up and released into the cytosol. Strikingly, cytochrome c treatment had a dramatically reduced effect on DCs from mutant mice relative to their wild-type counterparts. “This is the most sensitive in vivo assay to show antigen translocation to the cytosol,” says Udono. “This phenomenon was absent in HSP90á knockout mice, which makes me confident that our finding is important and has physiological relevance.”

Accordingly, Udono believes that molecules that modulate HSP90 activity might help clinicians to boost a patient’s immune counterattack against infection or cancer. “If we can control the expression levels of HSP90 and other heat shock proteins,” he says, “it could be of great benefit to human health.”

The corresponding author for this highlight is based at the Laboratory for Immunochaperones, RIKEN Research Center for Allergy and Immunology

gro-pr | Research asia research news
Further information:
http://www.riken.jp
http://www.researchsea.com

More articles from Life Sciences:

nachricht The dense vessel network regulates formation of thrombocytes in the bone marrow
25.07.2017 | Rudolf-Virchow-Zentrum für Experimentelle Biomedizin der Universität Würzburg

nachricht Fungi that evolved to eat wood offer new biomass conversion tool
25.07.2017 | University of Massachusetts at Amherst

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Carbon Nanotubes Turn Electrical Current into Light-emitting Quasi-particles

Strong light-matter coupling in these semiconducting tubes may hold the key to electrically pumped lasers

Light-matter quasi-particles can be generated electrically in semiconducting carbon nanotubes. Material scientists and physicists from Heidelberg University...

Im Focus: Flexible proximity sensor creates smart surfaces

Fraunhofer IPA has developed a proximity sensor made from silicone and carbon nanotubes (CNT) which detects objects and determines their position. The materials and printing process used mean that the sensor is extremely flexible, economical and can be used for large surfaces. Industry and research partners can use and further develop this innovation straight away.

At first glance, the proximity sensor appears to be nothing special: a thin, elastic layer of silicone onto which black square surfaces are printed, but these...

Im Focus: 3-D scanning with water

3-D shape acquisition using water displacement as the shape sensor for the reconstruction of complex objects

A global team of computer scientists and engineers have developed an innovative technique that more completely reconstructs challenging 3D objects. An ancient...

Im Focus: Manipulating Electron Spins Without Loss of Information

Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.

For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...

Im Focus: The proton precisely weighted

What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.

To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Closing the Sustainability Circle: Protection of Food with Biobased Materials

21.07.2017 | Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

The technology with a feel for feelings

12.07.2017 | Event News

 
Latest News

NASA mission surfs through waves in space to understand space weather

25.07.2017 | Physics and Astronomy

Strength of tectonic plates may explain shape of the Tibetan Plateau, study finds

25.07.2017 | Earth Sciences

The dense vessel network regulates formation of thrombocytes in the bone marrow

25.07.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>