Thymic reprogramming: Systemic inflammation changes the cellular output of the thymus from T cells to NK cells and iron-binding myeloid cells

01 October 2020 → Ongoing
Regional and community funding: Special Research Fund
Research disciplines
  • Medical and health sciences
    • Gastro-enterology
    • Autoimmunity
    • Microbiome
    • Inflammation
    • Innate immunity
Thymic reprogramming: from T cell to NK cell production CITE-seq: single-cell RNA-seq and antibody-mediated immunophenotyping In vivo validation
Project description

IL-12 and IL-18 are synergistically acting cytokines that are involved in the pathology of both viral infection and sepsis. By culturing ex vivo thymic lobes from neonatal mice, I was able to investigate the cells exiting the thymus following IL-12 and IL-18 stimulation. Surprisingly, this cytokine combination led to the exit of a massive amount of NK cells and myeloid cells into the supernatant of the organ culture. We have been able to validate these results, using the cutting-edge single-cell RNA sequencing and antibody profiling technique (CITE-seq), electron microscopy and confocal time-lapse imaging. The finding that ex vivo cultured neonatal thymic lobes can shift their main output from T cells to NK cells or myeloid cells is novel and may constitute an overlooked, yet fundamental biological function of the thymus during systemic inflammation. In this project proposal, I want to phenotype the thymus-derived cells and determine their localization by adoptive transfer. Furthermore, I will investigate whether this thymic reprogramming occurs in murine models of systemic inflammation and track the thymus-exiting cells using fluorescent grafts. Finally, I will investigate the cellular imprinting in the thymic lobes using in silico modeling tools and functional assays. Altogether, our exciting data opens completely novel perspectives on the role of the thymus in pathophysiological responses and might be therapeutically exploited in inflammatory and infectious diseases.