Researchers at Heidelberg University Hospital have discovered a key mechanism involved in the inactivation of immune cells and which also has an effect on the body’s defences. They have discovered that certain oxygen compounds are produced in greater quantities in the body due to cancer, inflammation, or as a result of ageing processes, and that this leads to the alteration of a protein that controls the flexibility and adaptability of certain immune cells. These cells are then no longer able to carry out their different activities in the immune system.
The results from the research group led by Professor Dr. Yvonne Samstag, professor of cellular immunology at the Institute of Immunology at Heidelberg University Hospital (Managing Director: Professor Dr. Stefan Meuer), have been published in the September issue of the scientific journal Immunity.
Oxygen radicals alter the key protein cofilin
Prof. Dr. Yvonne Samstag, Department of Cellular Immunology at the Institute of Immunology, University Hospital Heidelberg. (Photo: University Hospital Heidelberg) Free oxygen radicals, so-called reactive oxygen species (ROS), are considered to be the cause of many diseases and ageing processes. It is known that certain immune cells, the macrophages, produce larger quantities of hydrogen peroxide (H2O2) in cancer patients. This results in the suppression of the T-cells which are needed to fight off cancer. “We have now been able to show how oxygen radicals damage T-cells on the molecular level,” said Professor Dr. Yvonne Samstag.
The oxygen radicals oxidise and interfere with the protein cofilin, which is a central integrator of T-cell activation and an actin-remodelling protein. Cofilin needs to bind to actin in order for T-cells to be activated. “If the T-cells are not activated, then the entire immune system suffers,” said Professor Dr. Yvonne Samstag.
Next research goal: cancer, inflammation, autoimmune diseases
The researchers want to find out when cofilin alterations play a role in chronic inflammatory reactions, tumour diseases and autoimmune diseases. “The oxidation state of cofilin may reflect how well the T-cells, and hence a patient’s immune system, function,” said Dr. Martin Klemke, a scientist in Professor Samstag’s team and first author of the paper.
This finding might potentially have a role to play in the diagnosis and therapy of cancer. One possible cancer treatment could be the counteraction of oxygen radicals and their effect on cofilin.
The results also have implications for further research in the field of autoimmune diseases, for example rheumatoid arthritis. “In contrast to tumour diseases, the treatment of autoimmune diseases focuses on attenuating the overactive immune system, rather than stimulating it,” said Dr. Martin Klemke explaining that oxidative stress and its effects would in this case have a positive outcome. The mechanism discovered by the Heidelberg experts may possibly also lead to new insights into the treatment of autoimmune diseases.