Regulatory T Cells, the "Blue Helmets" of the Immune System
The human immune system has developed various strategies to control the spreading of myriads of pathogens - bacteria, fungi, viruses and parasites - within the body and to prevent their pathogenic effect. Pathogen-specific immune cells (T and B lymphocytes) are produced on a random basis to recognize the numerous pathogens. This random mechanism, however, harbours the risk that by chance some cells are generated which do not recognize pathogens but self molecules and thereby might cause autoimmune diseases.
Although the vast majority of these self-reactive immune cells is already eliminated during the generation of the cells within a control procedure (this process is called "central tolerance"), some of these self-reactive cells which have escaped the elimination do exist in any human being. The immune system has developed various immune regulatory mechanisms ("peripheral tolerance mechanisms") to prevent these self-reactive cells from attacking the body's own cells and cause autoimmune diseases. Among these are regulatory T cells (Tregs), a subgroup of T lymphocytes, also called "suppressor cells". You can imagine these cells as blue helmets of the immune system, which are endowed with a robust mandate in order to prevent immune reactions against the body's own tissues and to interfere de-escalating within the body's defense and so prevent collateral damages. Due to their highly effective suppressor mechanisms the Tregs play an important role in an acutely balanced immune system: their absence can lead to severe autoimmune diseases, whereas too high numbers of Tregs might suppress the necessary and wanted immune response against tumors or invading pathogens. Since Tregs - in comparison to the presently used immune suppressive drugs - act in a more specific manner, hope is set upon the blue helmets of the immune system for the therapeutic intervention in autoimmune diseases (e.g. rheumatoid arthritis, diabetes or multiple sclerosis), graft-versus-host disease or for the acceptance of allografts. Also the deactivation of Tregs in order to allow an effective immune response against tumors or chronic infections is currently being discussed. We aim to extend our knowledge about the origin of Tregs, their properties and their mechanism of action in order to apply or modulate them for therapeutic purposes. This is the focus of our department "Experimental Immunology".
The transcription factor Foxp3 is an important molecule for the development and function of Tregs. This molecule is being produced almost exclusively in Tregs and is responsible for regulating those genes being important for the function of Tregs. Therefore Foxp3 is a master switch for Tregs. Within the project "Regulation of Foxp3 expression", we examine by cellular and molecular methods these molecules, signaling pathways and epigenetic mechanisms, which control the gene expression of Foxp3. Knowing this, we intend to selectively shut off the Treg function for the therapy of cancer patients and chronically infected persons on one hand and on the other hand to develop efficient methods for the generation of Tregs for the therapeutic application in autoimmune disease patients and allograft recipients.
Within the project "Foxp3+ Tregs in mucosal tolerance" we aim to clarify which influence the intestinal micro milieu has on the expansion and survival of Tregs, how Foxp3+ Tregs are generated within the gut mucosa and if the Tregs maintain suppressive properties under chronic-inflammatory conditions. The results of these studies will be a significant contribution for the therapeutic use of Foxp3+ Tregs to cure chronic-inflammatory intestinal diseases such as ulcerative colitis or crohn's disease.
The characteristics of Tregs in solid tumors are the focus of our research within the project "Tregs and tumor-specific immune responses". By means of new transgenic mouse models we want to analyze the role of Foxp3+ Tregs for the suppression of tumor-specific immune responses, how Tregs get into the tumor, whether they are generated de novo and how they survive within the tumor. These results will be the basis for the development of new concepts to modulate of Foxp3+ Tregs in order to increase the immune response against tumors effectively.
Viewed as a whole we expect to get a better understanding of the cellular and molecular characteristics of Foxp3+ Tregs with this basic research in order to develop novel therapeutic concepts for the treatment of autoimmune diseases, chronic infections, tumors and to increase the allograft acceptance.