Abstract
The lymphatic system plays crucial roles in immunity far beyond those of simply providing conduits for leukocytes and antigens in lymph fluid. Endothelial cells within this vasculature are distinct and highly specialized to perform roles based upon their location. Afferent lymphatic capillaries have unique intercellular junctions for efficient uptake of fluid and macromolecules, while expressing chemotactic and adhesion molecules that permit selective trafficking of specific immune cell subsets. Moreover, in response to events within peripheral tissue such as inflammation or infection, soluble factors from lymphatic endothelial cells exert “remote control” to modulate leukocyte migration across high endothelial venules from the blood to lymph nodes draining the tissue. These immune hubs are highly organized and perfectly arrayed to survey antigens from peripheral tissue while optimizing encounters between antigen-presenting cells and cognate lymphocytes. Furthermore, subsets of lymphatic endothelial cells exhibit differences in gene expression relating to specific functions and locality within the lymph node, facilitating both innate and acquired immune responses through antigen presentation, lymph node remodeling and regulation of leukocyte entry and exit. This review details the immune cell subsets in afferent and efferent lymph, and explores the mechanisms by which endothelial cells of the lymphatic system regulate such trafficking, for immune surveillance and tolerance during steady-state conditions, and in response to infection, acute and chronic inflammation, and subsequent resolution.
Highlights
As with leukocyte recruitment via high through endothelial venules (HEV), CC-chemokine ligand 21 (CCL21) and chemokine receptor 7 (CCR7) are crucial for egress both T-cells and dendritic cells (DCs) from peripheral tissue [24,61,62,63,64,65,66], Table 1, whereas CCL19 is dispenof both T-cells and - DCs from peripheral tissue [24,61,62,63,64,65,66], Table 1, whereas CCL19 is sable [67,68]
Seventy years have passed since the first studies on leukocyte trafficking in the lymphatics, and our knowledge of the roles that the lymphatic system plays in immunological processes has expanded greatly
We can appreciate the complexity of lymph nodes, in which stromal cells including lymphatic endothelial cells (LECs) provide directional cues to ensure that leukocyte subsets home to specific locations, sampling antigen and responding to inflammatory stimuli and potential pathogens while maintaining tolerance for non-harmful exogenous and endogenous antigens
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Macromolecules and leukocytes exit the tissue via blind-ended afferent lymphatic vessels and enter draining lymph nodes via the subcapsular sinus. Lymph nodes are critical for immune surveillance, providing a highly organized hub in which blood-derived naïve lymphocytes might encounter antigen and antigen-presenting cells borne in the afferent lymph. After percolating through the lymph node, fluid and lymphocytes return to the blood circulation through efferent lymphatic vessels and the thoracic duct. There is selectivity as to which leukocytes are permitted to enter the lymphatic system and this review details the molec of 33 ular regulation of this, that imposed by endothelial cells of high endothelial venules, lymphatic vessels and lymph node sinuses
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