Developmental Immunology

The focus of the research of the Laboratory of Developmental Immunology is to delineate the molecular and cellular pathways that govern regular thymus organogenesis and function. Specifically, the lab is interested in the genetic and epigenetic control of the TEC differentiation and function. Using gene targeting we have generated unique tools that allow compartment-specific, experimental gain- and loss-of-function models in mice to interrogate aspects of thymus development and function at the cellular and molecular level. A special interest of our research is focused on understanding the epigenetic “code” that defines the regulatory principles in gene expression in TECs and the transcriptional programs that determine their cellular fate. Taking advantage of different molecular methods, we have begun to analyze the gene expression profile and the DNA methylation pattern of specific TEC subpopulations (eventually at single cell resolution), demonstrating striking differences of the latter when comparing cortical with medullary epithelia. The importance of miRNA for the development and maintenance of epithelial stroma is being investigated in mice where either Dicer or single miRNA are deleted in TEC. These mice reveal severe morphological changes in the composition and architecture of the thymic microenvironment leading to a reduced positive thymic selection and as a consequence to a T cell repertoire that elicits autoimmunity.