In addition to forming the myelin sheath along peripheral nerves and supporting neighbouring neurons, Schwann cells have also been found to play an important immune modulating function, starting and shutting off inflammation. This function not only helps nerve repair, but may also turn nerve tumours benign. These new findings were reported in the journal Glia.
The research has revealed that Schwann cells produce signalling molecules that can activate other immune cells. In particular, however, they are able to stop inflammatory reactions in order to prevent excessive tissue damage and allow the nerve to regenerate.
“This is essential, because inflammation releases free radicals against which nerve fibers cannot protect themselves. Therefore, the inflammation must be cleared quickly, which is precisely what Schwann cells do,” explained study designer Dr. Sabine Taschner-Mandl, who designed the study and heads a research group at St. Anna CCRI.
Do Schwann cells protect against malignancy?
These findings also have implications for protection against malignancy After nerve injury, Schwann cells engage a ‘repair’ mode that is also found in benign infantile nerve tumours. There, it causes the tumour cells to mature and thus reach a stage where they lose their aggressive properties and no longer divide unchecked
“Based on the current results, we now suspect that the immune cell functions of Schwann cells also become effective in childhood nerve tumours. This is because in cancer, there is always a kind of inflammation bubbling away that never comes to a halt. In benign nerve tumours, ganglioneuromas, the accompanying chronic inflammation could be stopped by Schwann cells similar to nerve healing, because unlike malignancies, ganglioneuromas have many Schwann cells in their microenvironment. We also see that a lot of immune cells migrate into these tumours, for which the Schwann cells could also be responsible,” said Dr Taschner-Mandl.
Healthy Inflammation: First Activate, Then Shut Down
In particular, the current study shows that Schwann cells can influence T cells, which are key in cancer defence. Schwann cells – both those in nerve regeneration and those in benign tumours – carry MHC-I and MHC-II molecules on their surface that are important for T-cell regulation. Via these molecules, Schwann cells present recognition features of material they have previously taken up from their environment.
“We mimicked an inflammatory response in the laboratory and detected a whole range of additional stimulatory and inhibitory surface molecules that are also necessary for T cell activation,” explained Jakob Berner, MSc, co-first author of the study and interim PhD student at St. Anna CCRI. “Our experiments show that Schwann cells are able to take up large amounts of material via phagocytosis.”
As the first immune response to a nerve cut, Schwann cells secrete substances that attract T cells, macrophages and other immune cells. Now it turned out that not only a reaction between the classical immune cells takes place, but also between Schwann cells and T cells.
While Schwann cells initially fuel the inflammatory response by releasing interferon-gamma, they can later shut it down by up-regulating the T-cell inhibitory PD-L1 molecule.
“First activate, then shut down – that’s the normal process of an inflammatory response. If this were also the case in cancer, then it could curb cancer growth,” Dr Taschner-Mandl theorised. Researchers are now investigating whether and how these findings could be applied to cancer treatment.
