Researchers uncover TRAT1's central role in T helper cell function

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. On the one hand, it dampens excessive immune activity, but at the same time it strengthens the targeted immune suppression by regulatory T cells."

Klaus Schmetterer, Study Leader and Professor, Medical University of Vienna

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. https://www.meduniwien.ac.at/web/en/ueber-uns/news/2025/news-in-october-2025/new-insights-into-the-control-of-the-immune-system-trat1-protein-acts-as-a-switch-between-defence-and-self-regulation/