Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Researchers Elucidate Transport Pathway of Immune System Substances

To transport substances from the site of their production to their destination, the body needs a sophisticated transport and sorting system.

Various receptors in and on the cells recognize certain molecules, pack them and ensure that they are transported to the right place. One of these receptors is Sortilin. It is present in the cells of the nervous system, the liver, and the immune system.

Studies by Stefanie Herda and Dr. Armin Rehm (Max Delbrück Center, MDC, and Charité) and the immunologist Dr. Uta Höpken (MDC) have now shown that the receptor Sortilin plays an important role in the function of the immune system (Immunity, doi: 10.1016/j.immuni.2012.07.012)*.

In the search for diseases, the T cells of the immune system go on patrol throughout the body. If they encounter a cell infected by viruses, they bind to it and secrete substances that ensure that the target cell dies. One of these substances is granzyme A, which penetrates the infected cell and induces programmed cell death. In addition, the immune cells secrete interferon-gamma, which induces the surrounding cells to have a stronger immune response.

Interferon-gamma is produced by cytotoxic T cells (formerly: T killer cells), T helper cells and natural killer cells. It enhances the activity of immune cells and induces other cells of the body to increasingly present fragments of the pathogen on their surface so that the T cells can find the affected cells more easily. To facilitate the transport of interferon-gamma from the interior of the T cell where it is produced to the cell membrane where it can be released, the cell uses its interior processing and transport system, to which the Golgi apparatus belongs.

If one were to imagine the Golgi apparatus as a post office, Sortilin’s task is to wrap the interferon-gamma cargo into these packages and navigate them to their destination. Without Sortilin, however, the packages cannot be delivered and remain in the post office, that is in the Golgi apparatus. Correspondingly, in the serum, i.e. outside of the cell, too little interferon-gamma is present. Thus, lack of interferon-gamma is not caused by diminished production, but rather by reduced or abrogated transport activity, eventually preventing the interferon-gamma from reaching its destination. This in turn leads to a weakened immune defense system since the interferon can only exert its immune-stimulating effect when it is released from the immune cells.

While the transport of interferon-gamma is disturbed in the absence of Sortilin, the transport of granzyme A, which destroys diseased cells directly, is more effective. Granzyme A uses another transport pathway, which is dependent on a multi-part receptor complex. This complex includes the molecule VAMP7. Together with its binding partners, this molecule ensures that transport packages containing granzyme A as part of its cargo reach their correct address in the cell. The work of the researchers led by Dr. Rehm suggests that Sortilin has an indirect influence on VAMP7 by promoting transport routes that lead to the degradation of VAMP7. In cells lacking Sortilin the researchers were able to detect increased VAMP7. This condition allowed for a more efficient transport and therefore an increased release of granzyme A.
Accordingly, Sortilin influences two different transport pathways for key immunological effector molecules in an opposite manner. Without Sortilin, less interferon-gamma is available, instead there is an increased level of granzyme A. But the increased concentration of granzyme A cannot compensate for the interferon gamma deficiency. In the experiment, the immune system of mice in which the researchers had deactivated Sortilin was significantly weaker and the fight against viruses and bacteria was less effective. The advantage for these animals, however, was that autoimmune diseases – that is, diseases in which one’s own immune system reacts against the body – were much less pronounced.

*The sorting receptor Sortilin exhibits a dual function in exocytic trafficking of interferon-γ and granzyme A in T cells

Stefanie Herda1, Friederike Raczkowski2, Hans-Willi Mittrücker2, Gerald Willimsky3, Kerstin Gerlach1, Anja A. Kühl4, Tilman Breiderhoff5, Thomas E. Willnow5, Bernd Dörken1,6, Uta E. Höpken7, Armin Rehm1,6

1 Max-Delbrück-Center for Molecular Medicine (MDC); Department of Hematology, Oncology and Tumorimmunology, 13125 Berlin, Germany
2 Institute for Immunology, University Medical Center, 20246 Hamburg-Eppendorf, Germany
3 Charité- Universitätsmedizin Berlin, Institute of Immunology, 12200 Berlin, Germany
4 Charité- Universitätsmedizin Berlin, Department of Pathology/Research Center Immuno Sciences, 12200 Berlin, Germany
5 Max-Delbrück-Center for Molecular Medicine (MDC); Department of Molecular Cardiovascular Research, 13125 Berlin, Germany
6 Charité- Universitätsmedizin Berlin, Department of Hematology, Oncology and Tumorimmunology, 13353 Berlin, Germany
7 Max-Delbrück-Center for Molecular Medicine (MDC); Department of Tumor- and Immunogenetics, 13125 Berlin, Germany

Barbara Bachtler
Press Department
Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch
in the Helmholtz Association
Robert-Rössle-Straße 10; 13125 Berlin, Germany
Phone: +49 (0) 30 94 06 - 38 96; Fax: +49 (0) 30 94 06 - 38 33

Barbara Bachtler | Max-Delbrück-Centrum
Further information:

More articles from Life Sciences:

nachricht First time-lapse footage of cell activity during limb regeneration
25.10.2016 | eLife

nachricht Phenotype at the push of a button
25.10.2016 | Institut für Pflanzenbiochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Enormous dome in central Andes driven by huge magma body beneath it

25.10.2016 | Earth Sciences

First time-lapse footage of cell activity during limb regeneration

25.10.2016 | Life Sciences

Deep down fracking wells, microbial communities thrive

25.10.2016 | Earth Sciences

More VideoLinks >>>