Explore our Research
Type 1 Diabetes is an autoimmune disease with a dramatically increasing incidence, particularly in childhood. It results from a breakdown in immune tolerance that causes the autoimmune-mediated destruction of the insulin-producing beta cells in the pancreas and a subsequent loss of glycemic control. We aim to advance our understanding of the immune mechanisms underlying Type 1 Diabetes development. Our overall vision is to contribute to the development of immune therapies that can decelerate or even halt autoimmune progression and prevent diabetes complications.
Regulatory T (Treg) cells are a distinct subset of CD4+ T cells and function as key cellular players for the maintenance of peripheral immune tolerance. Therefore, this classical function of Treg cells is crucial for the regulation of immune homeostasis and consequently, lack or functional deficiency of Treg cells contributes to the development and progression of autoimmune disorders such as Type 1 Diabetes. Furthermore, recent studies including our own, highlight a second, non-classical function of Treg cells: Their regulatory potential is not restricted to immune homeostasis, but also plays an important role for the regulation and maintenance of tissue homeostasis. These findings illustrate the unique potential of Treg cells for the development of novel precision immunotherapies that target autoimmune inflammation and/or tissue regeneration and remodeling. Therefore, our research comprises both classical and non-classical functions of Treg cells with the goal to dissect and target these cells in metabolic tissues of diabetes.
In the field of classical Treg cell function, we apply several key research approaches for dissecting and targeting of Treg cells. First, we aim to better understand the mechanisms that promote islet autoimmunity and its progression to Type 1 Diabetes. By characterizing autoantigen-specific T cell and Treg cell responses during islet autoimmunity in humans and mice, we identified multiple impairments in Treg cells as key drivers of the autoimmune reaction.
In line with our strong translational approach, we develop novel humanized mouse models which enable the dissection of human immune responses in vivo. This is not limited to human immune cells but also includes the interaction of these cells with important target cells of the autoimmune reaction, such as beta cells.
To further characterize and mechanistically dissect these Treg cell impairments we employ several independent approaches. Using sequencing-based microRNA screening, we showed that microRNAs in T cells function as important mediators of Treg cell impairments and as critical drivers of islet autoimmunity. Furthermore, we used extensive phenotyping approaches to define Treg cell dysfunction, instability and plasticity during islet autoimmunity. A broad spectrum of single-cell sequencing techniques, including novel bioinformatics tools, allows us to better understand the heterogeneity and functional specialization of Treg cells. These combined approaches also enable the identification of pathways involved in impaired immune regulation and potential targets for future intervention and therapeutic strategies.
Accordingly, we directly use these findings for the development of next generation Treg cell targeting strategies. That includes novel T cell-specific miRNA modulation strategies, combinatorial approaches of antigen-specific tolerance induction as well as novel pharmacological approaches to specifically induce Treg cells in settings of high immune activation and an independent approach to limit overshooting T cell activation.
As mentioned above, a second pillar of our research addresses non-classical Treg cell functions in metabolic tissues of diabetes. Here, we aim to advance our understanding of the heterogeneity and functional specialization of Treg cells in these metabolic tissue niches such as the pancreas, muscle, adipose tissue and the brain. To do so, we focus on environmental immune-metabolic cues to dissect molecular determinants how Treg cells unite their diverse functions with metabolic tissue integrity and function.
We strive to integrate these findings into understanding mechanisms of Treg cells in diabetes. These studies have the overarching translational goal of developing the next generation of precision immunotherapies that target autoimmune inflammation to decelerate or even halt autoimmune progression and/or foster metabolic tissue function and regeneration to restore tissue homeostasis.
Type 1 Diabetes is an autoimmune disease with a dramatically increasing incidence, particularly in childhood. It results from a breakdown in immune tolerance that causes the autoimmune-mediated destruction of the insulin-producing beta cells in the pancreas and a subsequent loss of glycemic control. We aim to advance our understanding of the immune mechanisms underlying Type 1 Diabetes development. Our overall vision is to contribute to the development of immune therapies that can decelerate or even halt autoimmune progression and prevent diabetes complications.
Regulatory T (Treg) cells are a distinct subset of CD4+ T cells and function as key cellular players for the maintenance of peripheral immune tolerance. Therefore, this classical function of Treg cells is crucial for the regulation of immune homeostasis and consequently, lack or functional deficiency of Treg cells contributes to the development and progression of autoimmune disorders such as Type 1 Diabetes. Furthermore, recent studies including our own, highlight a second, non-classical function of Treg cells: Their regulatory potential is not restricted to immune homeostasis, but also plays an important role for the regulation and maintenance of tissue homeostasis. These findings illustrate the unique potential of Treg cells for the development of novel precision immunotherapies that target autoimmune inflammation and/or tissue regeneration and remodeling. Therefore, our research comprises both classical and non-classical functions of Treg cells with the goal to dissect and target these cells in metabolic tissues of diabetes.
In the field of classical Treg cell function, we apply several key research approaches for dissecting and targeting of Treg cells. First, we aim to better understand the mechanisms that promote islet autoimmunity and its progression to Type 1 Diabetes. By characterizing autoantigen-specific T cell and Treg cell responses during islet autoimmunity in humans and mice, we identified multiple impairments in Treg cells as key drivers of the autoimmune reaction.
In line with our strong translational approach, we develop novel humanized mouse models which enable the dissection of human immune responses in vivo. This is not limited to human immune cells but also includes the interaction of these cells with important target cells of the autoimmune reaction, such as beta cells.
To further characterize and mechanistically dissect these Treg cell impairments we employ several independent approaches. Using sequencing-based microRNA screening, we showed that microRNAs in T cells function as important mediators of Treg cell impairments and as critical drivers of islet autoimmunity. Furthermore, we used extensive phenotyping approaches to define Treg cell dysfunction, instability and plasticity during islet autoimmunity. A broad spectrum of single-cell sequencing techniques, including novel bioinformatics tools, allows us to better understand the heterogeneity and functional specialization of Treg cells. These combined approaches also enable the identification of pathways involved in impaired immune regulation and potential targets for future intervention and therapeutic strategies.
Accordingly, we directly use these findings for the development of next generation Treg cell targeting strategies. That includes novel T cell-specific miRNA modulation strategies, combinatorial approaches of antigen-specific tolerance induction as well as novel pharmacological approaches to specifically induce Treg cells in settings of high immune activation and an independent approach to limit overshooting T cell activation.
As mentioned above, a second pillar of our research addresses non-classical Treg cell functions in metabolic tissues of diabetes. Here, we aim to advance our understanding of the heterogeneity and functional specialization of Treg cells in these metabolic tissue niches such as the pancreas, muscle, adipose tissue and the brain. To do so, we focus on environmental immune-metabolic cues to dissect molecular determinants how Treg cells unite their diverse functions with metabolic tissue integrity and function.
We strive to integrate these findings into understanding mechanisms of Treg cells in diabetes. These studies have the overarching translational goal of developing the next generation of precision immunotherapies that target autoimmune inflammation to decelerate or even halt autoimmune progression and/or foster metabolic tissue function and regeneration to restore tissue homeostasis.
