Immune cell crosstalk in barrier-defective skin driving systemic atopic disease (C11*)

• Subject Area: Dermatology ; Clinical Immunology and Allergology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 246807620

Skin barrier defects are a major cause of systemic atopy, but how compromised epithelial function translates into pathological type 2 immune bias remains unclear. BALB/c mice lacking two epithelial barrier proteins, FLG and TMEM79, defects of which are associated with atopy in humans, develop dermatitis, high IgE titers and asthma and constitute a relevant model for human atopic disease resulting from skin barrier defects. We will elucidate how information on the breached barrier is transmitted to the dermis and from there to the lymph nodes, instructing pathogenic type 2 responses. We will analyze dermal tissue by flow cytometry and single cell RNA sequencing. We identify migrated cells in the lymph nodes that arrived from the skin, to pinpoint gene expression patterns unique to migrated cells from barrier-defective skin. We will compare our findings to the human situation. As a novel approach to prevent atopy, we will evaluate skin microbiome modulation by probiotic colonization.

• 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. Axel Roers