Organ-specific lymphatic endothelial heterogeneity in tissue homeostasis and allergic inflammation

Lymphatic vessels resolve inflammation by draining cells, molecules and fluid. However, lymphatic endothelium also releases an array of molecules that are unique to each organ. These molecules could modify the inflammatory response, particularly T cell activation and differentiation. I will explore this in my Accelerator Award in health and during allergic inflammation, where homeostasis is disrupted, but the role for lymphatic vessels is unknown. I will isolate human lymphatic endothelium from different organs to identify their unique molecular signatures, before manipulating these molecules to assess their effect on T cell differentiation and function using ‘lymphatic-on-a-chip’ technology. By conditionally deleting these molecules from mice, and performing 3D mapping or single-cell transcriptomics, I will examine how T cell activation and differentiation are modified by lymphatic endothelium in healthy mouse organs. This will be repeated in mice with allergic inflammation of lungs or skin to see how organ-specific lymphatic endothelium influences the induction, severity and resolution of allergic disease. These experiments could inform therapeutic strategies for allergic inflammation and may teach us how to harness organ-specific lymphatic vessels in diseases. During this Award, I will also address barriers for medical doctors who, like me, commit to scientific research early in their careers.