Cookie Settings

We use cookies to optimize our website. These include cookies that are necessary for the operation of the site, as well as those that are only used for anonymous statistic. You can decide for yourself which categories you want to allow. Further information can be found in our data privacy protection .

Essential

These cookies are necessary to run the core functionalities of this website and cannot be disabled.

Name Webedition CMS
Purpose This cookie is required by the CMS (Content Management System) Webedition for the system to function correctly. Typically, this cookie is deleted when the browser is closed.
Name econda
Purpose Session cookie emos_jcsid for the web analysis software econda. This runs in the “anonymized measurement” mode. There is no personal reference. As soon as the user leaves the site, tracking is ended and all data in the browser are automatically deleted.
Statistics

These cookies help us understand how visitors interact with our website by collecting and analyzing information anonymously. Depending on the tool, one or more cookies are set by the provider.

Name econda
Purpose Statistics
External media

Content from external media platforms is blocked by default. If cookies from external media are accepted, access to this content no longer requires manual consent.

Name YouTube
Purpose Show YouTube content
Name Twitter
Purpose activate Twitter Feeds

How dying cells prevent dangerous immune reactions

No. 03 | 09/01/2020 | by Rei

Dying cells in the body can keep the immune system in check, thus preventing unwanted immune responses against the body's own tissues. Scientists of the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) have now identified a receptor on immune cells that activates this protective mechanism. This prevents dangerous autoimmune reactions in which the immune system is directed against the body's own structures, as the researchers have now been able to show in mice and human cells.

© Shutterstock

Billions of cells die every day in the human body. This occurs as part of a highly regulated process called apoptosis or programmed cell death. The dying cells confront the immune system with large amounts of proteins, which ought to activate an immune response, but the apoptotic cells seem to actively suppress the immune system so that it does not attack the body's own tissues. "We began wondering many years ago what kind of protective mechanism prevents autoimmune reactions – the body attacking its own tissues – when cells in the immune system, such as dendritic cells, take up the remains of the dead cells," Peter Krammer, an immunologist at the German Cancer Research Center (DKFZ), remarked.

Krammer, his colleague Heiko Weyd, and their team recently found an answer to the question: As soon as apoptosis is triggered, the dying cells transport proteins from the annexin family to the cell surface. The annexins act like a stop signal for the cells of the immune system and prevent an immune response from being triggered.

Kevin Bode from Krammer's department has now identified the dectin-1 protein as the annexin-binding receptor on the surface of dendritic cells: Dectin-1 recognizes the annexins and triggers a signaling pathway in dendritic cells that ultimately suppresses the immune response.

Mice that do not have any dectin-1 on the surface of their dendritic cells showed a stronger immune response to dying, apoptotic cells. Moreover, the mice without dectin-1 developed signs of autoimmune diseases in old age.

DKFZ researchers have discovered how apoptotic cells prevent dangerous immune reactions.
© DKFZ

The DKFZ scientists thus discovered an important control mechanism for the immune system's 'self-tolerance'. "But we assume that the body has other protective functions to prevent autoimmune reactions too. That's why the loss of dectin-1 in the animals does not become apparent until later in life," Bode explained.

"Interestingly, dectin-1 has a dual role," added Peter Krammer. Dectin-1 not only binds annexins; it also binds certain pathogens at a different binding site. This has the opposite effect and triggers an immune response. "We thus identified a crucial immune checkpoint which, depending on the binding partner, either triggers or suppresses the immune response," Krammer explained, emphasizing the importance of the work.

A key link in the dectin-1 signaling pathway is the enzyme NADPH oxidase 2. People who lack this enzyme develop autoimmune diseases. In cooperation with the Children's Hospital Zurich and Heidelberg University Hospital, the DKFZ researchers are therefore currently examining blood samples from patients lacking NADPH oxidase 2 to find new starting points for potential treatments.

Why animal experiments are vital in cancer research

Autoimmune diseases have a hugely detrimental impact on patients' lives and in some cases are even life-threatening. In order to develop effective treatments, it is therefore vital to know which mechanisms suppress the immune responses to a patient's own body tissues or in contrast activate them. By establishing the interaction between annexin on the surface of dying cells and dectin-1 on the dendritic cells, Bode and his colleagues identified a key mechanism that prevents autoimmune reactions in healthy body tissues. In doing so, they have found an interesting starting point for future drug treatments.

Although the interactions between annexin and dectin-1 were initially identified in a Petri dish, the scientists needed an animal – with all the diversity of the various components of the immune system – to demonstrate that the bond between these two proteins actually suppresses autoimmune reactions.

Kevin Bode, Fatmire Bujupi, Corinna Link, Tobias Hein, Stephanie Zimmermann, Diluka Peiris, Vincent Jaquet, Bernd Lepenies, Heiko Weyd and Peter H. Krammer: Dectin-1 binding to annexins on apoptotic cells induces peripheral immune tolerance via NADPH oxidase-2

CELL Reports DOI: 10.1016/j.celrep.2019.11.086

With more than 3,000 employees, the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) is Germany’s largest biomedical research institute. DKFZ scientists identify cancer risk factors, investigate how cancer progresses and develop new cancer prevention strategies. They are also developing new methods to diagnose tumors more precisely and treat cancer patients more successfully. The DKFZ's Cancer Information Service (KID) provides patients, interested citizens and experts with individual answers to questions relating to cancer.

To transfer promising approaches from cancer research to the clinic and thus improve the prognosis of cancer patients, the DKFZ cooperates with excellent research institutions and university hospitals throughout Germany:

  • National Center for Tumor Diseases (NCT, 6 sites)
  • German Cancer Consortium (DKTK, 8 sites)
  • Hopp Children's Cancer Center (KiTZ) Heidelberg
  • Helmholtz Institute for Translational Oncology (HI-TRON Mainz) - A Helmholtz Institute of the DKFZ
  • DKFZ-Hector Cancer Institute at the University Medical Center Mannheim
  • National Cancer Prevention Center (jointly with German Cancer Aid)
The DKFZ is 90 percent financed by the Federal Ministry of Education and Research and 10 percent by the state of Baden-Württemberg. The DKFZ is a member of the Helmholtz Association of German Research Centers.

RSS-Feed

Subscribe to our RSS-Feed.

to top
powered by webEdition CMS