In the fight against cancer or chronic infections, the immune system must be active over long periods of time. However, in the long run, the immune defence system often becomes exhausted. Scientists at the German Cancer Research Center (DKFZ) have now found initial evidence in mice that skeletal muscles help to keep the immune system functional in chronic diseases.
In many cases, severe weight loss and a decrease in muscle mass are the result of cancer or dangerous infections. In addition to this process known as cachexia, patients often suffer from a weakened immune system. One of the reasons for this is a loss of function of a group of T-cells, whose task it is to recognize and kill virus-infected cells or cancer cells.
The processes leading to loss of T-cell activity are still largely unexplained. However, first indications suggest that there is a connection with cachexia. "It is known that T-cells are involved in the loss of skeletal muscle mass. But whether and how, in turn, skeletal muscles influence the function of the T-cells is still unclear," explains Guoliang Cui from the DKFZ.
To find out, the scientists infected mice with lymphocytic choriomeningitis virus (LCMV). This method is a widely used model system to study the course of acute or chronic infections in mice. The researchers then analysed the gene expression in the skeletal muscles of the animals and found that in chronic infections, the muscle cells release an increased amount of the messenger substance interleukin-15. This cytokine causes T-cell precursors to settle in the skeletal muscles. As a result, they are spatially delimited and protected from contact with the chronic inflammation.
"If the T-cells, which actively fight the infection, lose their full functionality through continuous stimulation, the precursor cells can migrate from the muscles and develop into functional T-cells," said Jingxia Wu, lead author of the study. "This enables the immune system to fight the virus continuously over a long period."
So could regular training strengthen the immune system? "In our study, mice with more muscle mass were better able to cope with chronic viral infection than those whose muscles were weaker. But whether the results can be transferred to humans, future experiments will have to show," explains Guoliang Cui.
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Wu J, Weisshaar N, Hotz-Wagenblatt A, Madi A, Ma S, Mieg A, Hering M, Mohr K, Schlimbach T, Borgers H and Cui G: Skeletal muscle antagonizes antiviral CD8+ T cell exhaustion. Science Advances 2020; DOI: 10.1126/sciadv.aba3458
The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) with its more than 3,000 employees is the largest biomedical research institution in Germany. More than 1,300 scientists at the DKFZ investigate how cancer develops, identify cancer risk factors and search for new strategies to prevent people from developing cancer. They are 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 all questions on cancer.
Jointly with partners from the university hospitals, the DKFZ operates the National Center for Tumor Diseases (NCT) in Heidelberg and Dresden, and the Hopp Children's Tumour Center KiTZ in Heidelberg. In the German Consortium for Translational Cancer Research (DKTK), one of the six German Centers for Health Research, the DKFZ maintains translational centers at seven university partner locations. NCT and DKTK sites combine excellent university medicine with the high-profile research of the DKFZ. They contribute to the endeavor of transferring promising approaches from cancer research to the clinic and thus improving the chances of cancer patients.
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.
Journal
Science Advances