Institut für Medizinische Mikrobiologie und Hygiene

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Forschungsgebiete

Introduction

The focus of our lab is to understand the role of transcription factors in lymphocyte development and function. Ultimately, this analysis will lead to the identification of new regulatory pathways, which can be translated into clinical practice. Thus, our lab has a strong interest in basic immunology while at the same time trying to transfer knowledge from “bench to bedside”.

The developmental program and the effector function of different lymphocyte subsets are determined by transcription factors, which coordinate a regulated program of gene expression. This in turn implicates that the differential expression or the specific combination of transcription factors can serve as a hallmark for different lymphocyte subsets. How transcription factors can have such lineage defining capacity is one of the major challenges in biology.

T-box Transcription

The transcription factors (TFs) T-bet and Eomesodermin (Eomes) regulate type 1 immune responses in innate (e.g. natural killer cells) and adaptive lymphocytes (e.g. activated CD8 T cells). Such responses are broadly characterized by the signature cytokine IFN-γ and cytotoxic effector function against intracellular pathogens and tumors. T-bet and Eomes both belong to the large and diverse T-box TF family, that all share the evolutionary conserved DNA-binding domain, the T-box. T-box TFs are present in all metazoans and play important roles in cell fate decisions and organogenesis during development. T-box genes can be grouped into five subfamilies and genes within the same subfamily have arisen from duplication of a single ancestral gene. T-bet and Eomes together with Tbr1 belong to the Tbr1 subfamily and are thus paralogs that share a high degree of sequence homology, especially within their T-box domains. As a result, they exert partial functional redundancy during viral infection. However, the actual degree of redundancy between T-bet and Eomes remains a matter of debate and is further confounded by their distinct spatiotemporal expression pattern in activated CD8 T cells.

Using transcription factor specific transgenic mouse models in combination with high-throughput state-of-the-art analytic tools (e.g. scRNA sequencing, multidimensional immunofluorescence) we strive to get a detailed understanding of the spatial and temporal induction of the two T-box transcription factors to unravel their distinct roles in different lymphocyte subsets.

Tissue resident immune cells in renal autoimmunity and transplantation

Another focus of the lab is to understand the effector phase of an immune response that leads to end organ damage. Initial priming of adaptive immune cells usually happens in secondary lymphoid organs or the spleen but ultimately, immune cells have to migrate into their target organ, where they become tissue resident, to execute their effector functions. In addition, these cells act in concert with other tissue resident immune cells (e.g. innate lymphoid cells, macrophages) to amplify tissue damage.

In the clinical setting, we do not see the patient at the “priming stage” but rather at that is late time point, where organ involvement and dysfuntion is already evident. Hence, a thorough analysis of the specific characteristics of these tissue resident cells, which differs profoundly from circulating immune cells, will guide us in developing new therapeutic targets that can mitigate immune-related renal diseases.