Iron regulation and oxidative stress in systemic sclerosis (C05)

• Subject Area: Dermatology ; Rheumatology
• Term: since 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 246807620

We have identified inflammatory monocyte recruitment into the skin and the glutathione and ferroptosis regulating antiporter system xCT (Slc7a11) as critical mechanisms of oxidative stress-induced cutaneous fibrosis in mouse models of systemic sclerosis (SSc) and in the skin of SSc patients. In the next funding period, we will focus on monocyte-fibroblast interaction during ROS-triggered fibrotic responses and address glutathione and ferropotosis related pathways in fibroblasts as key parameters in fibrosis development. Our project uses in vivo experiments and translational settings with skin explants from SSc patients, human 3D skin equivalent models (HSE) and a new preclinical humanized SSc mouse model (MISTRG) to identify and validate potential therapeutic target molecules for SSc.

• DFG Programme: CRC/Transregios
• Subproject of: TRR 156: The skin as sensor and effector orchestrating local and systemic immunity
• Applicant Institution: Ruprecht-Karls-Universität Heidelberg
• Project Heads: Privatdozentin Dr. Verena Raker; Professor Dr. Detlef Schuppan, until 6/2019; Professorin Dr. Kerstin Steinbrink