Lymph node lymphatic endothelial cells as multifaceted gatekeepers in the immune system

Single-cell technologies have recently allowed the identification of multiple lym-phatic endothelial cell (LEC) subsets in subcapsular, paracortical, medullary, and other lymph node (LN) sinus systems in mice and humans. New analyses show that LECs serve key immunological functions in the LN stroma during immune re-sponses. We discuss the roles of different LEC types in guiding leukocyte and cancer cell trafficking to and from the LN parenchyma, in capturing microbes, and in transporting, presenting, and storing lymph-borne antigens in distinct types of lymphatic sinuses. We underscore specific adaptations of human LECs and raise unanswered questions concerning LEC functions in human dis-ease. Despite our limited understanding of human lymphatics - hampering clin-ical translation in inflammation and metastasis - we support the potential of LN LECs as putative targets for boosting/inhibiting immunoreactivity.

Automated summary

Single-cell technologies have revealed multiple subsets of lymphatic endothelial cells (LECs) in the lymph node sinus systems of mice and humans. These LECs play important immunological roles in the lymph node stroma, including guiding immune cell trafficking, capturing microbes, and transporting lymph-borne antigens. However, our understanding of LEC functions in human disease is still limited, hindering clinical translation in inflammation and metastasis. Nonetheless, targeting LECs in the lymph nodes has potential for modulating immune reactivity in these conditions.