Regulation of Th cell differentiation by MAZR

1 T cells, also called T lymphocytes, belong to a group of white blood cells and exert 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 the FWF, 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. In further studies we will now examine in detail, by using a variety of molecular biological and immunological methods, how MAZR regulates this subset of T cells. Through these studies we expect not only a better understanding of the regulation of immune cells, but also medically interesting insights into the immune system.

T cells, also called T lymphocytes, belong to a group of white blood cells and exert important functions in the immune system. They are divided into two main subsets, the CD4+ T helper cells and CD8+ cytotoxic T cells. Both subsets arise in the thymus from common progenitor cells, known as CD4/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 research 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? We had preliminary results that indicated that MAZR plays an important role for the generation and function of regul atory 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. In the course of this FWF project we examined in detail, by using a variety of molecular biological and immunological methods, how MAZR regulates this subset of T cells. In an experimental approach in which the Mazr gene was deleted in T cells and therefore switched -off, we observed that MAZR inactivation increased the numbers of re gulatory T cells. In contrast, enhancing MAZR function experimentally resulted in a decrease of regulatory T cell numbers. Moreover, deleting MAZR in T cells reduced the clinical score of DSS-induced colitis, which is an inflammatory disease of the gut, suggesting that the inhibition of MAZR might be beneficial for certain types of immune-mediated diseases, perhaps via regulating regulatory T cell function. Taken together, our study revealed that MAZR is a key molecule in the fine regulation of the development of regulatory T cells.