SFB TRR 156: The skin as sensor and effector orchestrating local and systemic immunity

Basic data for this project

Description

Recent advances in cutaneous research have documented that skin is not only an important barrier organ, but also fulfills major immune functions locally and systemically. In the past, the skin immune system has primarily been investigated from narrow perspectives, e.g. by studying a specific cell subtype or model disease. This falls short of understanding the highly complex molecular and cellular interactions in the skin and subsequently has led to unnecessary delays in the development of novel therapies for skin diseases. The goal of this consortium, which is unique in its focus and composition worldwide, is to understand skin immunity in its complexity in order to generate the basis for future therapies. To achieve this goal, dermatologists, immunologists, microbiologists and biochemists from three sites work together in a coherent consortium and work program to gain a better understanding of the skin immune system. To approach these aims, three interconnected research areas were defined. The focus of area A is to define the role of molecules and microbes challenging the skin immune system from outside and mainly deals with innate immune reactions. Here especially the study of the skin microbiome has led to the identification of novel molecules (e.g. lugdunin) and cells (e.g. innate lymphoid cells (ILC)) steering the interactions of the skin immune system with microbes such as Staphylococcus (S.) aureus. The focus of area B is the intercellular crosstalk of cells and molecules within skin. Here a major focus is on antigen-presentation and resulting T cell responses leading to adaptive immunity. The projects in area B contributed to a better understanding of the role of keratinocytes, certain DC-subtypes and their role in the regulation of inflammation in disease models such as contact hypersensitivity (CHS) and psoriasis. Area C focusses on the effect of skin immune reactions for triggering autoinflammatory diseases such as psoriasis, autoimmune blistering disease, or scleroderma and provided groundbreaking results on their pathogenesis. Most projects, however, have overlapping activities in multiple areas. The transfer of our scientific achievements into clinical practice remains the major goal for the next two funding periods.