The thymus is the only tissue capable of supporting the development of functional, yet self-tolerant T lymphocytes. The T cell “educational program” in the thymus is primarily orchestrated by thymic epithelial cells (TECs), which provide the desired microenvironment for T cell differentiation and selection (reviewed in Kadouri N, et al, Nat Rev Immunology, 2019). Therefore, one of the primary goals of the Abramson lab is to better understand the functional and molecular heterogeneity of the TEC compartment and to further elucidate the molecular mechanisms controlling TEC differentiation into different functionally-defined cell subsets. Indeed, by utilizing single cell transcriptomics, our lab has made several seminal discoveries, in which we identified various novel TEC populations, including thymic tuft cells (Borstein C, et al, Nature,2018), thymic endocrine cells or thymic microfold cells. More importantly, we have also demonstrated that each of these novel TEC subsets plays a distinct functional role ranging from induction of central tolerance to regulation of thymus homeostasis (Givony T, et al, Nature, 2023) to facilitation of thymus regeneration after injury (Nevo S, et al, Sci Immunol, 2024). Furthermore, in a parallel set of studies, we have successfully deciphered transcriptional mechanisms controlling the expression of the thymus “master regulator” - FOXN1 (Kadouri N, et al, Sci Immunol, 2022) or programs regulating TEC development and differentiation (in progress).
