Klinik für Hautkrankheiten

The incidence of skin diseases is continuously rising in the western countries. An estimated 15-20% of the general population suffers from an allergic contact dermatitis (ACD) leading to distress of the affected patients and high socio-economical costs. Despite progress in elucidating the pathogenesis of this T cell-mediated allergic skin disease, efforts to target and develop effective and specific therapeutic strategies are still missing. Therefore, we have focused on the analysis of allergen (hapten)-specific immune responses in two different models: the contact hypersensitivity reaction (CHS), resembling the ACD in humans, and low zone tolerance (LZT), mimicking a physiologic mechanism for prevention of ACD development. The aim of this project is the analysis of mechanisms of the innate immune system and their interactions with adaptive immune responses in hapten-specific T cell-mediated skin reactions of LZT and CHS. We focus on the molecular (PRR), cellular (myeloid cells) and on microbiome-induced mechanisms for the development of skin inflammation. The identification of key elements of the innate immune system may result in the development of innovative therapeutic approaches for cutaneous diseases.

This project is funded by the German Research Foundation (DFG) with the CRC1009 “Breaking Barriers” https://www.medizin.uni-muenster.de/sfb-1009.

In cooperation with several groups of the Cell-in-Motion Interfaculty Center Münster multiscale- imaging techniques will be combined with nanoparticle-based methods to unravel mechanisms of the innate immune system during the early phase of autoimmune diseases such as systemic Lupus erythematosus (SLE) and systemic sclerosis (SSc). This cooperation project (with K. Landfester, Max-Planck Institute for Polymeric Research, Mainz) is funded by the German Research Foundation (DFG) within the CRC1450 “inSight” https://www.uni-muenster.de/CRC-inSight/research/area-C/C06.php.

The hallmark of the pathogenesis of scleroderma (Scl), the skin manifestation of systemic sclerosis, is fibrosis development. However, the function of monocyte/macrophage differentiation and of dendritic cells during the early phase of cutaneous fibrosis is not clear. We will alter the frequency, polarization and migration of myeloid/dendritic cells to test Scl development and the underlying immune mechanisms in chemically induced and spontaneous models of the disease. In addition, we will compare these data with that of monocytes/myeloid cells in the blood and the skin of patients suffering from systemic sclerosis to identify key (innate) cellular myeloid drivers and dominant molecular mechanisms of fibrosis development.

This cooperation project (with Verena Raker, Department of Dermatology, University of Münster) is funded by the German Research Foundation (DFG) within the TR156 “The Skin as Sensor and Effector Organ” https://www.klinikum.uni-heidelberg.de/sfbs/sfb-trr156/welcome.

Cell-type specific drug delivery by use of nanoparticles has become a promising approach for induction of efficient cancer immunotherapy. However, attempts to boost the immune system against the tumour often fail as tolerance induction within the tumour microenvironment plays a critical role in cancer progression and tremendously weakens the success of cancer immunotherapy. In this context, the axis of IL-10-/STAT3-mediated tolerance processes play a pivotal role. Therefore, we will modulate STAT3-mediated tumour-associated mechanisms by use of STAT3 inhibitor-loaded functionalized nanocapsules. We will analyse the impact on tolerogenic DC and myeloid cells and, in particular, on T cells (regulatory FOXP3⁺, cytotoxic CD8⁺ T cells), thereby taking advantage of the established method of IL-2 functionalized nanocapsules for T cell targeting. Further studies will unravel the therapeutic effect of our nanocapsule-based systems in models of malignant melanoma in vivo.

This project (cooperation with Katharina Landfester, Max Planck Institute for Polymeric Research, Mainz) is funded by the German Research Foudndation (DFG) within the CRC1066 “Nanodimensional Polymeric Therapeutics for Cancer Therapy” https://sfb1066.de/.