Cell Death and Inflammation in the Skin

Cell death and inflammation in the skin

The skin constitutes the first protective barrier of the organism, protecting it against water loss and external physical, chemical, and biological insults such as wounding, UVB radiation, and microorganisms. The skin exists of an outer squamous epithelium, the epidermis, and inner connective tissue, the dermis. The skin barrier is mainly constituted by upper terminal differentiated keratinocyte layers of the epidermis. Keratinocytes are epithelial cells constituting the major cell type in the epidermis. The epidermis is continuously rejuvenated by proliferating keratinocytes in the basal layer to reduce the risk of accumulating damaged cells (e.g. by UV irradiation). Imbalances in the delicate physiological turn-over of proliferating or differentiating keratinocytes can result in the disturbance of the skin barrier function or control of keratinocyte proliferation and are reflected in many skin disorders, such as psoriasis, eczema, cancer, etc.

Our research group tries to understand the role of molecules involved in homeostasis, cell death and inflammation in the skin. Therefore, we developed substantial expertise in the field of molecular signal transduction in cell death and inflammation using in vitro and in vivo model systems (about 140 publications in the field of expertise). Currently, we focus on studying the molecular signal transduction pathways in keratinocytes involving RIP kinase 4 (RIPK4). RIPK4 plays a major role in the skin by regulating keratinocyte differentiation and cornification. Based on genetic evidence from our and other research groups RIPK4 mainly acts as a tumor suppressor in the skin. However, how RIPK4 governs this biological function is currently unclear and an area of ongoing research.

Areas of Expertise

• Cell death and NF-κB signaling
• In vivo mouse gene targeting and development of skin inflammation mouse models
• Study of the molecular pathways involving caspases and RIP kinases

Technology Transfer Potential

• Development of mouse models for inflammatory skin diseases
• Identification of therapeutic targets in cell death and inflammation

Selected publications

• Urwyler-Rösselet, C. et al. Functions of the RIP kinase family members in the skin. Cell Mol Life Sci. 80, 285 (2023). Visit ➚
• Devos, M. et al. Sensing of endogenous nucleic acids by ZBP1 induces keratinocyte necroptosis and skin inflammation. J Exp Med. 217, e20191913 (2020). Visit ➚
• Devos, M. et al. Keratinocyte Expression of A20/TNFAIP3 Controls Skin Inflammation Associated with Atopic Dermatitis and Psoriasis. J Invest Dermatol. 139, 135-145 (2019). Visit ➚
• Tanghe, G. et al. RIPK4 activity in keratinocytes is controlled by the SCFβ-TrCP ubiquitin ligase to maintain cortical actin organization. Cell Mol Life Sci. 75, 2827-2841 (2018). Visit ➚
• Urwyler-Rösselet, CI et al. Keratinocyte-Specific Ablation of RIPK4 Allows Epidermal Cornification but Impairs Skin Barrier Formation. J Invest Dermatol. 138, 1268-1278 (2018). Visit ➚

Bibliography

• Full bibliography Visit ➚