Wnt-associated Dkk3 in inflammatory and fibrosing skin disease (C06)

• Subject Area: Dermatology ; Rheumatology
• Term: from 2019 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 246807620

Radiation dermatitis can initiate a chronic inflammatory/fibrosing process. We found that Dickkopf-3 (Dkk3), a Wnt-related protein linked to immune regulation, promotes chronic fibrosing inflammation in mouse models of radiation damage. Dkk3 knockouts do not develop epidermal hyperplasia, or chronic dermal fibroblast/inflammatory activation. The proposal seeks to (i) identify the relevant cellular source of Dkk3 in radiation damaged skin using reporter mice and targeted Dkk3 knockouts, (ii) characterize Dkk3 effects on local macrophages and T cells, (iii) dissect the impact of Dkk-related signalling pathways using human skin models, and (iv) connect radiation-induced epigenetic modifications to expression of Dkk3 and chronic inflammatory fibrosis.

• 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: Professor Dr. Peter Jon Nelson; Privatdozent Dr. Roger Sandhoff