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LET´s play MARCO polo in the LECs pool
By Ruben Grosso
25 May, 2020
Fluorescent labelling of lymphatic endothelial cell (LEC) populations in a mouse inguinal lymph node (LN). All LECs share expression of the pan LEC marker PROX1 (blue). The lymphatic marker LYVE1 (red) mark the floor of the subcapsular sinus (SCS) (fLECs) and major areas of the paracortical and medullary sinuses while the ceiling of the SCS (cLECs) is negative. MARCO-LECs are distinguished from other LN LECs by their high expression of the scavenger receptor Macrophage Receptor with Collagenous Structure (MARCO) (green). MARCO staining delineates medullary sinuses adjacent to the B cell follicles in the LN (peri-follicular sinuses).
Lymph nodes (LN) are important sentinel organs where adaptive immune response takes place. Structurally, the LN is composed of a complex lymphatic vascular network surrounded by mesenchymal stromal and immune cells. The lymphatic vessels allow the peripheral immune cells and inflammatory molecules to reach their respective targets within the LN. This is the basis for a correct immune cell interaction and activation. The LECs that lines these vessels are the first cells encountering antigens, immune cells/molecules, microorganisms and tumor cells. Thus, LECs are adapted to constant changes induced by immunological stimuli and in response of neighboring cells types.
In collaboration with Eugene Butcher’s lab at Stanford University, we have used single-cell sequencing to describe five conserved LN LECs population in mouse and human LN: valve LECs, ceiling-LECs, floor-LECs and two previously not defined, paracortical and medullary LEC populations: Ptx3-LECs and MARCO-LECs. I mapped these subsets in situ by microscopy to understand their spatial distribution as illustrated in the picture. Each population has unique, niche-specific, gene expression profiles indicating their high specialization with distinct pathways for immune interactions and matrix re-modelling.
This work has provided valuable new information about the versatility and organ-specific functions of LECs and provides a basis for our continued work, in which we explore the phenotypic changes of the LN vasculature in disease. The latter includes studies to understand the molecular interactions between the LN lymphatic vasculature and invading tumor cells in LN metastasis.
About the author:
Ruben Grosso is a researcher in Maria Ulvmar’s group at IGP. His work is centered around the identification of new LEC subtypes in the LN and on learning more about their roles and phenotypic changes in inflammation and in cancer.
Dept. Immunology, Genetics and Pathology
Rudbeck Laboratory C11
Dag Hammarskjölds Väg 20
751 85 Uppsala