Researchers at the Medical University of Vienna have taken a closer look at a previously largely unknown component of the immune system: the protein molecule TRAT1 (T Cell Receptor Associated Transmembrane Adaptor 1) plays a central role in how so-called T helper cells (a specialised subgroup of immune cells) distinguish between attack and self-control – an important mechanism for restraining inflammation and preventing autoimmune diseases. The findings have recently been published in the journal Cell Communication and Signaling.

T helper cells are the "conductors" of the immune defence, controlling the function and specialisation of other immune cells and thus "tailoring" the immune response to the respective pathogen. The T helper cell compartment is divided into effector T helper cells, which actively fight intruders, and regulatory T cells (Treg), which prevent an excessive immune response. Until now, only part of how this balance is controlled was understood. A research team at the Medical University of Vienna, led by Ralf Schmidt and Klaus Schmetterer (Department of Laboratory Medicine), has now been able to show that TRAT1 acts like a switch in these processes. In the "attack" cells (effector T cells), TRAT1 ensures that activation proceeds in a controlled manner. If TRAT1 is switched off using the CRISPR/Cas9 gene editing tool, these cells become more active but lose their ability to produce certain inflammatory messengers such as interleukin-17. In the "protective" cells (Treg), on the other hand, TRAT1 supports their inhibitory function – but in a complex way: it enhances the suppression of other immune cells, but not uniformly for all cell types. "Our data show that TRAT1 is a dual regulator of the immune system," explains study leader Klaus Schmetterer. "On the one hand, it dampens excessive immune activity, but at the same time it strengthens the targeted immune suppression by regulatory T cells."

However, these results, which were determined in cell culture, also have high clinical relevance: altered expression patterns of TRAT1 were found in data series of immune cells from patients with graft-versus-host disease (GvHD) and systemic lupus erythematosus. This suggests that signal filtering in T helper cells is defective in these diseases. "In the long term, these findings could also help to develop new cell-based immunotherapies – such as tailor-made CAR-Treg cells that specifically prevent unwanted immune reactions. We have already been able to prove this in a novel 3-dimensional cell culture model for transplant rejection," explains Tobias Frey, first author of the study.