Microbiota-dependent expression of IL22 by group 3 innate lymphoid cells regulates skin mesenchymal and epithelial cell differentiation (A02)

• Subject Area: Medical Microbiology and Mycology, Hygiene, Molecular Infection Biology ; Dermatology ; Immunology
• Term: since 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 246807620

ILC3 produce effector molecules such as the cytokine IL22 that regulate differentiation and function of non-hematopoietic cells in tissues, expanding the range of immune system functions. The commensal Staphylococcus (S.) aureus controls IL22 production by skin ILC3 which required expression of S. aureus virulence factors. Analysis of mice genetically lacking IL22 revealed a previously unappreciated role of IL22 for the differentiation of skin mesenchymal and epithelial cells. Using a combination of genetic barcoding, spatially resolved scRNA-seq and imaging, we will study the effect of S. aureus colonization on ILC3 function and localization, and we will interrogate how IL22 affects epithelial and mesenchymal cell differentiation. Finally, given the unexpected effects of IL22 on fibroblast differentiation and function, we will address the role of IL22 in mouse models of tissue damage and fibrosis.

• 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. Andreas Diefenbach; Professorin Dr. Christiane Wolz, until 6/2023