MAZR function in CD4+ T lymphocytes and in mast cells

My long-term scientific goal is to understand transcriptional networks that control CD4/CD8 cell fate choice. Moreover, we are interested to understand whether these networks also regulate peripheral T cell differentiation/function. We have recently identified that the zinc finger protein MAZR is an important regulator of Cd8 gene expression and CD4/CD8 cell fate decision during T cell development. MAZR is a newly identified transcription factor, and therefore not much is known about the role of MAZR in peripheral T cells and in other cells of the immune system. Since many transcriptional regulators implicated in CD4/CD8 cell fate choice have also important regulatory function in peripheral T cells subsets, we investigated whether MAZR has also a role in helper T cells. Using conditional gene targeting approaches, we have obtained preliminary evidence that MAZR regulates Th17 differentiation as well as mast cell function. Based on these findings, we propose to study the function of MAZR in the differentiation of CD4+ effector T cell subsets, and to investigate the role of MAZR in mast cells. We expect that our studies will reveal novel insight into the function of MAZR beyond T cell development.

T cells, also called T lymphocytes, belong to a group of white blood cells that execute important functions in the immune system. They are divided into two main subsets, the CD4+ T helper cells and the CD8+ cytotoxic T cells. Both T cell subsets arise in the thymus from common progenitor cells, known as the CD4 and CD8 double-positive (DP) thymocytes. How is it decided whether a DP cells develops into a T helper cell or into a cytotoxic T cell? Which factors play a role in this decision? How do T helper cells specialize during an immune response, so that they can carry out different functions? Are factors that regulate T cell development also involved in controlling the differentiation of peripheral T helper cells? These are some of the many important issues in the field of immunology that fascinate many scientists, since they address fundamental biological and immunological processes.During the last couple of years our group made important contributions to answer some of these questions. We have shown that the transcription factor MAZR (transcription factors regulate the production of RNA from DNA templates) is one of the factors that regulate the decision whether DP thymocytes develop into either CD4+ or CD8+ T cells. To identify additional functions of MAZR in T cells, we have started to investigate whether MAZR regulates peripheral CD4+ T cells: Is MAZR involved in the differentiation of CD4+ T cells into effector CD4+ T cells? Which subsets of T helper cells are regulated by MAZR? Does MAZR influence the development of immunological diseases? And can we identify factors that function together with MAZR? Our preliminary results, obtained with funding from this FWF project, indicate that MAZR plays an important role for the generation and function of regulatory T cells. Regulatory T cells are a subset of T helper cells that suppress the activation of auto-reactive T cells and thus prevent the development of autoimmune diseases. These data provide also the basis for a new FWF project application. In addition, we identified that MAZR is involved in the regulation of mast cells, which are an important effector immune cell population causing also allergic immune reactions. Thus, our studies defined also a role for MAZR in the regulation of immune cells beyond T cells.