Immune cells turn damage into repair

Intestines one week after abdominal irradiation, showing proliferating epithelial cells (in brown).
Image Credit: Julius Fischer / TUM 

Patients receiving intensive cancer treatments often suffer from severe damage to the intestinal lining. Researchers from the Technical University of Munich (TUM) and the Leibniz Institute for Immunotherapy (LIT) have discovered that certain immune cells can trigger healing processes. They use inflammatory signals to do so - which is surprising, as inflammation in the intestine was previously thought to be primarily harmful. This finding could open new possibilities for therapies. 

Regulatory T cells (Tregs), a specialized type of immune cells, are usually seen as “peacekeepers” that prevent excessive immune attacks. In a study  published in Signal Transduction and Targeted Therapy, researchers from the Department of Radiation Oncology at the TUM University Hospital and the LIT Cooperation Group “Innate Immune Sensing in Cancer and Transplantation” uncovered how the body's own immune system can be harnessed to repair the intestinal lining and improve survival.  

Until now, inflammation in the intestine was primarily considered harmful. “Now we have seen that under certain conditions the immune system uses inflammatory signals for starting healing,” Prof. Hendrik Poeck, Managing Senior Physician at the Clinic and Polyclinic for Internal Medicine III at University Hospital Regensburg (UKR) and Head of the LIT Cooperation Group “Innate Immune Sensing in Cancer and Transplantation”, summarizes the results. “These findings could have important clinical implications for many patients undergoing cancer treatments that harm the intestine,” explains Dr. Julius Fischer, first and corresponding author of the study, research group leader, and specialist in radiation oncology at the TUM School of Medicine and Health at TUM University Hospital. 

Klinikum Dr. Julius Fischer (right) and his research group for radioimmunooncology
Photo Credit: Kathrin Czoppelt / TUM 

Two molecules with combined effects 

PhD student and first author of the study, Sascha Göttert, from the Clinic and Polyclinic for Internal Medicine III at UKR, discovered that in both mouse models and patient samples, Tregs produce two inflammation-associated molecules that work together to stimulate intestinal stem cells: “We found that interferon-gamma, IFNγ for short, and interleukin-10 – IL-10 – act in concert to influence the gut’s natural repair units,” explains Göttert. While IFNγ alone triggers rapid cell growth but exhausts the intestinal stem cell pool, and IL-10 alone provides only weak support, their combination delivers a powerful yet sustainable repair signal. This cooperation supports both rapid healing and long-term regeneration of the gut following immune- and radiation-related injuries, such as after stem cell transplantation or abdominal irradiation.  

Patients receiving intensive cancer treatments - such as radiation or stem cell transplantation - often suffer from severe damage to the intestinal lining. “This not only causes painful inflammation and infectious complications but also worsens long-term clinical outcomes,” says Dr. Julius Fischer. Following the results, the immune system`s own repair program seems to play an important role in protecting the gut during cancer therapy: “This study highlights the interplay of intestinal stem cells and Tregs that release immune signaling molecules as master repairers for injured tissues,” Prof. Hendrik Poeck, Head of the LIT Cooperation Group “Innate Immune Sensing in Cancer and Transplantation” constats. Uncovering these processes has the potential to enable new therapeutic strategies to promote intestinal repair. 

Published in journal: Signal Transduction and Targeted Therapy

Title: Tissue-adapted Tregs harness inflammatory signals to promote intestinal repair from therapy-related injury

Authors: Julius C. Fischer, Sascha Göttert, Maximilian Giller, Paul Heinrich, Kaiji Fan, Omer Khalid, Caroline N. Walther, Maria Drießlein, Sophie M. Nefzger, Gabriel Eisenkolb, Vincent R. Timnik, Sebastian Jarosch, Lena Klostermeier, Thomas Engleitner, Nicholas Strieder, Claudia Gebhard, Sarah Diederich, Nicole A. Schmid, Laura Lansink Rotgerink, Laura Joachim, Sakhila Ghimire, Eva Vonbrunn, Maike Büttner-Herold, Marianne Remke, Katja Steiger, Rupert Öllinger, Roland Rad, Daniel Wolff, Markus Feuerer, Petra Hoffmann, Matthias Edinger, Michael Rehli, Markus Tschurtschenthaler, Oliver Kepp, Guido Kroemer, Erik Thiele Orberg, Stephanie E. Combs, Wolfgang Herr, Florian Bassermann, Dirk H. Busch, Ernst Holler, Simon Heidegger, and Hendrik Poeck

Source/Credit: Technische Universität München

Reference Number: ongy112725_01

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