Coagulation receptors in models of cutaneous inflammation (C07)

• Subject Area: Immunology
• Term: since 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 246807620

We study the contributions of coagulation receptors to skin inflammation with a focus on the role of protease activated receptor (PAR) signaling and the endothelial cell protein C receptor (EPCR) in the autoimmune pathology of psoriasis. We have previously shown that coagulation signaling by PAR2 in myeloid cells is relevant for the development of the contact hypersensitivity reaction in mice and patients. We recently identified monocyte- and dendritic cell-expressed EPCR loaded with the lysosomal lipid LBPA as the pathogenic target for antiphospholipid antibodies in the toll like receptor (TLR) 7 mediated autoimmune pathology of lupus. We propose to study in mutant and cell type-specific knock-out mice how these coagulation-related signaling pathways regulate inflammation and contribute to psoriasis-like skin pathology in mice. Preclinical models will assess the effects of interventional therapeutic strategies targeting coagulation signaling complexes in ameliorating skin inflammation.

• 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 Head: Professor Dr. Wolfram Ruf