Lessons of Vascular Specialization From Secondary Lymphoid Organ Lymphatic Endothelial Cells

Abstract

Secondary lymphoid organs, such as lymph nodes, harbor highly specialized and compartmentalized niches. These niches are optimized to facilitate the encounter of naive lymphocytes with antigens and antigen-presenting cells, enabling optimal generation of adaptive immune responses. Lymphatic vessels of lymphoid organs are uniquely specialized to perform a staggering variety of tasks. These include antigen presentation, directing the trafficking of immune cells but also modulating immune cell activation and providing factors for their survival. Recent studies have provided insights into the molecular basis of such specialization, opening avenues for better understanding the mechanisms of immune-vascular interactions and their applications. Such knowledge is essential for designing better treatments for human diseases given the central role of the immune system in infection, aging, tissue regeneration and repair. In addition, principles established in studies of lymphoid organ lymphatic vessel functions and organization may be applied to guide our understanding of specialization of vascular beds in other organs.

Lymphatic Dysfunction Models an Autoimmune Emphysema Phenotype of Chronic Obstructive Pulmonary Disease

“…Flow cytometry confirmed surface expression of MHC II on a subset of LECs from the lungs of Clec2 pltKO mice and not in control mice (Figure 2f). This immunomodulatory subtype lacks costimulatory molecules that are typically found in antigen presenting cells (20) and has also been seen in other settings of impaired lymphatic function where TLOs form (18), suggesting that the presence of this LEC subtype may be a marker of impaired lymphatic drainage and inflammation in multiple settings.…”

Lymphatic System in Organ Development, Function, and Regeneration

“…Arroz-Madeira et al 24 review the molecular phenotypes of 5 distinct subsets of lymphatic endothelial cells within lymph nodes and their specialized roles in immune cell homeostasis, tolerance, and active inflammation. In addition, inflammation-induced changes in lymphatic endothelia, molecular plasticity, and the impact of circadian rhythms on lymphatic vessels and lymphoid organs are also discussed.…”

“…Recent advances in genetics and molecular profiling have revealed the distinct cellular composition of the lymph node outer cortex, paracortex, and medulla under normal and disease conditions. In the review, Arroz-Madeira et al 24 provide in-depth analyses of the heterogeneity of lymphatic endothelial cells within the lymph node and their specialized roles in lymph node function and development. Lymphatic endothelial cells occupy various niches of the lymph node, including the subcapsular sinus, paracortical/cortical sinuses, and medullary sinuses.…”

Mechanisms and functions of intestinal vascular specialization

“…However, its expression is restricted rapidly after birth to a subset of LN lymphatic vessels, GALT HEVs, and villus/crypt HEV-like venules ( Fig. 4 B ; Arroz-Madeira et al, 2023 ; Salmi et al, 2001 ). In early postnatal and adult mice, MADCAM1 expression is promoted by the transcription factors NKX2-3 and COUP-TFII ( Dinh et al, 2022 ; Kellermayer et al, 2014 ; Pabst et al, 2000 ; Pabst et al, 1999 ; Wang et al, 2000 ).…”