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.
Highlights
Cells in complex vertebrates receive signals from extracellular environment which coordinate a raft of important cellular programs and functions [1]
Results derived from microarray studies of Lymphatic endothelial cell (LEC) isolated from in vivo settings. ↑ relatively higher, ↓ relatively lower mRNA expression in first vs. second disease/tissue setting
We recently identified a cooperative role for CCL27, CCL28, and their receptor CCR10 in VEGF-D driven tumor lymphangiogenesis [44]
Summary
Cells in complex vertebrates receive signals from extracellular environment which coordinate a raft of important cellular programs and functions [1]. While having a conserved three-stranded β-sheet/α-helix tertiary structure they are divided into several subfamilies (CXC, CC, XC, and CX3C) based on variations in their quaternary structure and critical cysteine residues [4, 5]. They exert their effects through cell surface G-protein coupled receptors on target cells [4] that can act as homo- or heterodimers depending on the context. This family has expanded to include at least 51 chemokines and 20 receptors, plus (presently) four atypical or decoy receptors which typically dampen chemokine activity by binding and internalizing chemokines without initiating G-protein-dependent signaling [5,6,7]
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