Project Details
Projekt
Myeloid cell mediated vascular inflammation in psoriasis (C08)
Subject Area
Immunology
Dermatology
Dermatology
Term
since 2019
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 246807620
Psoriasis is associated with an increased prevalence of cardiovascular disease (CVD) and cardiovascular-driven mortality. We have previously shown that the cardiovascular comorbidity in murine Interleukin-17A driven psoriasis-like skin disease is associated with vascular inflammation mainly based on myeloid cells and with arterial hypertension. To gain a better understanding of CVD development in psoriatic mice we will investigate the myeloid cells invading the skin and the vessel wall of the psoriatic mice and compare them to myeloid cells in the Angiotensin II driven murine hypertension model. To this end, we will investigate the myeloid cells for the production of reactive oxygen species (ROS) and study their gene expression profile by single cell sequencing (scSeq) to determine their pathogenic potential. In parallel, we will investigate the impact of one additive cardiovascular risk factor CVRF (high fat diet) on vascular inflammation and on myeloid cells reactivity in psoriasis. In addition, we plan to investigate if and how cytokines produced in the skin can directly impact on CVD development and focus especially on IL-36. As a downstream cytokine of the IL-17 signaling cascade, IL-36 could also be relevant in chronic systemic inflammation in psoriasis vulgaris. Therefore, we plan to especially investigate if cytokines of the IL-36 family may link psoriasis to CVD and will use mice systemically and cell type-specifically deficient for the IL-36 receptor.
DFG Programme
CRC/Transregios
Applicant Institution
Ruprecht-Karls-Universität Heidelberg
