Development and structure of the lymphoid system

Summary of key facts

The lymphatic system is a complex, blind-ended vascular tree distinct and separate from the blood circulatory system.
Lymphatics facilitate tissue fluid homeostasis, nutrient uptake, and immune functions.
Lymphatic vessels and lymphatic endothelial cells have unique features promoting uptake and transport back to the blood circulation.
Lymphatic endothelial cell specification and differentiation are promoted by specific molecular programs.
Heterogeneity and plasticity of lymphatic endothelial cells help create specialized tissue- and organ-specific lymphatic vascular beds.
Lymph nodes are complex structures with unique layers of endothelial cells that function as key immune surveillance centers.
Lymphatic vessels are present in the tumor microenvironment where they are active in tumor metastasis.
Tumor-associated lymphatic vessels have distinct molecular profiles compared with normal lymphatic vessels.
Crosstalk between the lymphatic system and tumors is important for cancer progression and metastasis.
For example, VEGFC and VEGFD are major growth factors attracting VEGFR3-expressing lymphatic endothelial cells and accelerating tumor lymph angiogenesis.
Most of our current knowledge regarding the function of lymphatics in cancers is limited to a few cancer types such as melanoma, breast cancer, and glioblastomas, so there is much still to be explored.

Introduction

The vascular system in our body is essential for supplying nutrients, macromolecules, and cells to tissues and organs but also critical for efficiently removing waste products. The blood and lymphatic vascular systems are responsible for these roles. The lymphatic system is a blind-ended network of vessels that runs parallel to the blood vessels and collects fluid from interstitial spaces to return it back to the bloodstream. ^, Although the first description of lymph nodes and glands is found in the Hippocratic treatise “On glands” from around 400 BC, ^, the 17th century was the golden age for the investigation of the lymphatics with several key discoveries: gut lacteals, cloacal bursa, reservoir of the chyle, extraintestinal lymphatic vessels, and hepatic lymph circulation. ^, In the early 20th century, Florence Sabin and other classical anatomists characterized the lymphatic system in detail using dye injection and histology to characterize fluid uptake. In addition to its important function in tissue and systemic fluid homeostasis, the lymphatic system plays a vital role in immune surveillance by regulating production and transportation of immune cells in response to immunogenic stimuli. Moreover, certain organs contain specialized lymphatic networks that support their function. For example, lacteal lymphatics absorb fatty acids in the intestine and meningeal lymphatics regulate cerebral spinal fluid homeostasis. Therefore lymphatics play numerous important physiologic roles in human health, and lymphatic research is a rapidly emerging field in cardiovascular medicine.

In this chapter, we review structural, molecular, and functional aspects of lymphatic system development and further discuss the importance of understanding this system in oncology.

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