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.

T cells 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. Th cells play a central role in the coordination of the immune response. They are sub-divided into further subgroups essential for the fine-tuning the immune response to combat pathogens. However, Th cell subsets formation must be properly regulated, since dysregulation of Th cell differentiation can lead to immunological diseases such as autoimmunity or allergies. How are various Th cells generated during an immune response upon pathogen exposure? Which factors and regulatory networks play a role in these processes? How are Th subsets maintained? How does the immune system prevent incorrect differentiation pathways and which processes go wrong when this happens? Some of many important questions of basic immunological research that fascinate many scientists, since it is also about elucidating fundamental immuno(bio) logical processes. With support of FWF funding, our group made in recent years important contributions to answer some of these questions. We have shown that the transcription factor PATZ1/MAZR (transcription factors regulate the transcription of DNA into RNA) regulates the formation of CD4+ and CD8+ T cells. We also showed that PATZ1/MAZR has a key role in the formation and function of regulatory T cells, which are a subset of Th cells that are important for immune balance, as they can suppress potential autoreactive T cells and thus prevent the development of autoimmune diseases. If PATZ1/MAZR activity is reduced, more regulatory T cells are produced, and a higher PATZ1/MAZR activity decreases regulatory T cells. Interestingly, there are several forms of PATZ1/MAZR (these forms differ in molecular structure; these are called PATZ1/MAZR isoforms), but their exact functions are not known. Of note, PATZ1/MAZR not only has important functions in the immune system, but also plays an important role in the development of certain types of cancer. PATZ1/MAZR has also been shown to regulate important processes during embryonic development. Thus, it is important to understand how PATZ1/MAZR functions. With the support of this FWF-funded project, we have started to elucidate the functions of PATZ1/MAZR isoforms using a variety of molecular biology and immunological methods. Among many experimental approaches, we have also developed novel preclinical mouse models to understand the function of PATZ1/MAZR isoforms. For example, we have identified which isoforms are important for embryonic development. In further studies, we are now using these new models to gain a better understanding about the regulation of immune cells and to obtain medically interesting insights into the immune system, as well as to gain new insights into fundamental biological processes.