Leukocyte and Lymphatic Interactions at the Cribriform Lymphatics

Abstract There is mounting evidence that the lymphatic vessels surrounding central nervous system (CNS) play an important role in maintaining fluid homeostasis, antigen drainage, waste clearance, and steady-state immune cell migration from CNS. Recently we reported a murine mouse model of multiple sclerosis stroke during inflammatory brain disease large number dendritic cells (DCs) are recruited to cribriform lymphatics, near olfactory bulbs. These brain-derived DCs then bind LECs at plate (cp) retained vessel instead trafficking straight lymph nodes forming measurable DC-LEC aggregates. Here this study, attempted characterize these interactions, better understand binding events on neuroinflammatory disease. To accomplish performed series scRNAseq experiments which revealed neuroinflammation endothelial up-regulate several factors related leukocyte adhesion, processing/presentation, cytokine signaling. Additionally, data suggests many interactions could be immunoregulatory nature, modifying local population via PD-L1/PD1 axis. Together our suggest lymphatics represent immunological niche where response regulated. Supported by grants NIH 1R01NS126595-01A1