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PICTURE: Dietmar Zehn (right) with the first author of the new study on chronic immune responses, Francesca Alfei, and his collaborator, Markus Flosbach.
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Credit: D. Zehn / Technical University of Munich
Tumors and some viral infections pose a challenge to the human body that the immune system generally fails to manage. In these diseases, he goes to a hypofunctional state preventing adequate protection. A research team from the Technical University of Munich (TUM) has achieved major success: it has been able to identify the crucial molecular switch that triggers such dysfunctional immune responses. This could allow the future to disable or prevent this state.
Normally, the immune system goes into a state of maximum alert after a viral infection. It triggers the activation of a variety of immune cells such as T and B cells. These cells procreate in large numbers and aggressively fight infected cells. However, if the immune system fails to defeat the virus, the immune cells appear with strongly inhibited functions. This "depletion" of immune cells is triggered by the continuous activation of immune cells due to the virus. However, this attenuation of immune responses is also a positive advance for the body, as a strong and persistent immune response would be a major burden and a major cause of cell and tissue damage. Deactivation of immune responses can also allow massive growth of tumors.
The search for a mechanism
The stated goal of research on tumors and infections is to control or prevent the transition from a normal immune response to a dysfunctional immune response. Dietmar Zehn, Professor of Animal Physiology and Immunology at the TUM Faculty of Life Sciences at Weihenstephan, has been interested for years in this type of chronic immune response and in the mechanisms of molecular disabling. underlying.
"They represent the compromise of the body between the damage that would be caused by a strong immune response and the disease itself.We are fascinated by these mechanisms for several reasons: In addition to chronic infections, they also occur with tumors, have been Mechanically mediocre understood in the past, and in 2018, the Nobel Prize in Medicine was dedicated on this subject, "says Zehn, describing the importance of this area. "In particular, the demonstration made by colleagues at the University Hospital of Freiburg that Tox is correlated with T-cell dysfunction also in patients with chronic hepatitis C highlights the medical relevance of our observations."
Protein Tox activates the "mode of exhaustion"
Until now, it was vaguely known how the body activated and regulated these immune responses. Zehn and his team found the deciding factor at the same time as two groups in the United States. The study was published in the scientific journal Nature.
Tox protein is the decisive molecular switch. Using mouse and cell culture models as well as patient samples, scientists discovered that the protein had an effect on the cell nucleus, thus activating a genetic program that modifies the function of immune cells. As a result, inhibitory surface receptors appear on the surface of immune cells. The cells are thus open to inhibitory signals, ensuring that the cells "get tired", work less well or even die.
Useful in a variety of different therapies
"It is extremely important that we have finally decoded these molecular processes: this is the sine qua non condition for a targeted modification of the processes.Controlling Tox could allow to reactivate weak immune responses, which would be interesting for example to fight against tumors or slow down excessive immune responses like those found in autoimmune diseases, "says Dietmar Zehn.
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Publication:
Francesca Alfei, Kristiyan Kanev, Maike Hofmann, Ming Wu, Hazem E. Ghoneim, Patrick Roelli, Daniel T. Utzschneider, Madlaina von Hösslin, Jolie G. Cullen, Yiping Fan, Vasyl Eisenberg, Dirk Wohlleber, Katja Steiger, Doron Merkler , Mauro Delorenzi, Percy A. Knolle, Cyrille J. Cohen, Robert Thimme, Benjamin Youngblood and Dietmar Zehn: Tox reinforces the phenotype and longevity of depleted T cells in chronic viral infections, NatureJune 17, 2019, DOI: 10.1038 / s41586-019-1326-9
https: /
More information:
Web page of the Chair of Animal Physiology and Immunology of the TUM
http: // physio.
Profile of Prof. Dietmar Zehn
http: // www.
High resolution image
https: /
Contact:
Dr. Dietmar Zehn
Chair of Animal Physiology and Immunology
TUM Weihenstephan School of Life Sciences
Technical University of Munich (TUM)
Tel .: + 49 (0) 89 289 23325 (press office)
[email protected]
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