The pathogenic role of EBI2 in skin inflammation

• Applicant: Dr. Florian Kurschus, Ph.D.
• Subject Area: Dermatology ; Immunology
• Term: from 2020 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 444609457

The G-Protein coupled receptor EBI2 and its ligand 7α,25-dihydroxycholesterol (7α,25-OHC) form a chemotactic system acting in fine-positioning of immune cells in lymphoid organs in homeostasis and inflammation. In the EAE model we showed that EBI2 and its ligand also promote the transmigration of T cells into the inflamed target organ. Our preliminary data using contact hypersensitivity (CHS) as a model for allergic contact dermatitis (ACD) show that EBI2 is important for the disease to fully develop. Recently, it was shown that EBI2 and its ligand also play an important role in the formation of so-called tertiary lymphoid structures (TLS) in the lung (iBALT) and the gut (cryptopatches). Similar structures called inducible Skin-Associated Lymphoid Tissues (iSALT), have previously been described in the skin in the CHS model. Therefore, we want to investigate which pathogenic role EBI2 plays in acute, chronic and memory models of CHS. We will follow different, not mutually exclusive, hypotheses: 1. Is EBI2 important for priming of T cells in draining lymph nodes by migratory skin dendritic cells? 2. Are EBI2 and 7α,25-OHC important in the formation of iSALTs to promote skin inflammation? 3. Do EBI2 and its ligand play important roles in the transmigration of effector and memory T cells from the blood into the skin? Finally, we want to measure ligand production in the inflamed skin and to define which cells do express the ligand-generating enzymes during skin inflammation.

• DFG Programme: Research Grants