MAZR isoform-specific functions in T cells and beyond

1 T cells (also known as T lymphocytes) belong to the group of white blood cells and have important functions in the immune system. They are divided into two main types, the CD4+ T helper (Th) cells and the CD8+ cytotoxic T cells. T helper cells play a central role in the coordination of the immune response. They are sub- divided into further subgroups essential for the fine-tuning of the immune response in order to combat pathogens. However, the formation of Th cell subsets must be properly regulated, since dysregulation of Th cell differentiation can lead to immunological diseases such as autoimmunity or allergies. How are the various Th cells generated during an immune response upon pathogen exposure? Which factors and regulatory networks play a role in these processes? How are the Th subset maintained? How does the immune system prevent incorrect differentiation pathways and which processes go wrong when this happens? Some of the many important questions of basic immunological research and which fascinate many scientists, since it is also about elucidating fundamental immuno(bio) logical processes. With the support of several FWF projects our group has been able in the last couple of years to make important contributions to answering some of these questions. We have shown that the transcription factor MAZR (transcription factors regulate the writing of DNA into RNA) regulates the development of CD4+ and CD8+ T cells. We also showed that MAZR plays an important role in the development and function of regulatory T cells, a special subgroup of T helper cells. Regulatory T cells are important for immune homeostasis because they suppress potential autoreactive T cells and thereby prevent the development of autoimmune diseases. Our studies also revealed that if the function of MAZR is reduced, then more regulatory T cells are generated, while an increase in MAZR activity reduces regulatory T cell generation. Thus, MAZR controls regulatory T cell numbers. Of note, there are several forms of MAZR known in T cells and in other cells (these are also called MAZR isoforms, which differ in their molecular structure), however their individual functions are not know. In further studies, with supported of the FWF, we now plan to elucidate the functions of MAZR isoforms in detail using a variety of molecular biological and immunological methods. MAZR has important functions in the immune system, but is also implicated in the development of certain types of cancer. Furthermore, MAZR has also been shown to regulate important differentiation processes during embryonic development. We therefore expect that our studies not only provide a better understanding of the regulation of Th cells and reveal medically interesting insights into the immune system, but that they will also generate novel insights into fundamental biological processes in general.