The Interplay Between Lymphatic Vessels and Chemokines

Abstract

Chemokines are a family of small protein cytokines that act as chemoattractants to migrating cells, in particular those of the immune system. They are categorized functionally as either homeostatic, constitutively produced by tissues for basal levels of cell migration, or inflammatory, where they are generated in association with a pathological inflammatory response. While the extravasation of leukocytes via blood vessels is a key step in cells entering the tissues, the lymphatic vessels also serve as a conduit for cells that are recruited and localized through chemoattractant gradients. Furthermore, the growth and remodeling of lymphatic vessels in pathologies is influenced by chemokines and their receptors expressed by lymphatic endothelial cells (LECs) in and around the pathological tissue. In this review we summarize the diverse role played by specific chemokines and their receptors in shaping the interaction of lymphatic vessels, immune cells, and other pathological cell types in physiology and disease.

Keywords: chemokine; chemokine receptor; endothelial; lymphangiogenesis; lymphatic remodeling; lymphatics.

Figure 1

LECs contribute to the role of chemokines by acting as either the source or target cell. Chemokines are a structurally related family of cytokines that direct cell movement and are classified as XC, CC, CXC, or CX₃C chemokines depending on the positions of conserved cysteine residues which form disulfide bridges. Lymphatic endothelial cells (LECs) receive chemokine signals, using cell surface G protein-coupled receptors, from source cells which include cells of the immune system, other LECs, fibroblasts and pathological cells types such as cancer cells. LECs also act as the source of chemokines, secreting these proteins to act on chemokine receptors present on other target cells. Furthermore, LECs can regulate chemokine availability by scavenging and internalizing secreted chemokines via atypical or decoy chemokine receptors.