Lymphatic Endothelial Cells in Health and Disease

Area of Science:

• Vascular Biology
• Immunology
• Cell Biology

Background:

• Lymphatic endothelial cells (LECs) traditionally support fluid drainage and immune cell transport.
• Recent research reveals LECs are heterogeneous, adopting tissue- and disease-specific states.
• A comprehensive framework linking LEC origin, niche, and state transitions to function is needed.

Purpose of the Study:

• To review the developmental origins, identity maintenance, and anatomical distribution of LEC states.
• To discuss how specialized LEC states regulate lymphatic transport and immune surveillance in homeostasis.
• To examine LEC reprogramming in various diseases and highlight therapeutic opportunities.

Main Methods:

• This review synthesizes findings from lineage tracing, multiomics, functional imaging, and perturbation studies.
• It integrates data on LEC heterogeneity across the lymphatic network.
• The review focuses on a state-centered framework for LEC function.

Main Results:

• LECs exhibit diverse states that are crucial for tissue homeostasis and disease progression.
• Specialized LEC states coordinate fluid drainage, immune surveillance, and metabolic functions.
• Context-dependent LEC reprogramming contributes to lymphatic disorders, inflammation, cancer, and CNS dysfunction.

Conclusions:

• A state-centered framework reframes LECs as critical regulators of tissue homeostasis and disease.
• Understanding LEC heterogeneity offers a conceptual foundation for precision lymphatic medicine.
• Targeting specific LEC states holds translational potential for various diseases.