National Institute of Allergy and Infectious Diseases 5R01AI130471-09

Progenitor Cells for High Endothelium in the Immune Response

This NIH grant supports research on the mechanisms controlling the expansion and specialization of high endothelial venules (HEV) in immune responses, focusing on progenitor cells and molecular pathways involved in immune angiogenesis.

Description

High endothelial venules (HEV) are specialized portals for lymphocyte entry into lymphoid tissues and sites of chronic inflammation from the blood. Along with flat walled postcapillary venules, they regulate immune cell trafficking in physiologic and pathologic settings including autoimmune diseases, inflammation, and cancer. HEV in lymph nodes draining sites of immune challenge expand dramatically to support enhanced lymphocyte recruitment, with new high endothelial cells (HEC) arising by proliferation and by neogenesis from capillary resident progenitors (CRP). The molecular pathways that control HEV expansion and differentiation from capillary precursors are as yet unclear; but generation of a comprehensive atlas of lymph node blood endothelial cell subsets, molecular phenotypes, and responses to immune challenge now allows us to identify candidate pathways involved. Our fundamental focus in this renewal application is therefore to identify and characterize novel mechanisms of HEV specialization and generation in the immune response. We will mechanistically define pathways that (i) regulate progenitor cell homeostasis and transitional EC expansion in immune angiogenesis; (ii) induce the unique

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