The role of cellular metabolic pathways and the influence of the microbiome in the pathogenesis of psoriasis (B08)

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

Psoriasis is an immune-mediated inflammatory skin disease associated with other pathologies such as metabolic syndrome, non-alcoholic fatty liver disease, and dyslipidemia, suggesting that metabolic dysregulation may be at the core of the disease. In this project, we aim to understand how changes in microbes and metabolites can alter immune cell function and influence psoriasis pathology. For this, we will make use of a diet-exacerbated mouse model and a topical fatty acid synthesis inhibitor mimicking systemic and local metabolic changes described in patients with psoriasis. Dyslipidemia results in impaired lipid barrier function associated with alteration of the skin microbiome which will be analysed in detail. We will further validate our studies in human 3D skin models and biopsies from psoriasis patients, and complement our findings by exploring the contribution of intestinal dysbiosis to the development of skin disease in a clinical cohort of psoriasis patients. In summary, the current project aims to decipher the molecular mechanisms linking organismal to cellular metabolic disturbances and the role of the microbiome in psoriasis pathogenesis.

• 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. Tim Dominik Sparwasser; Professorin Dr. Sara Vieira-Silva, Ph.D., since 7/2023