Exploring the complex role of chemokines and chemoattractants in vivo on leukocyte dynamics

Abstract

SummaryChemotaxis is fundamental for leukocyte migration in immunity and inflammation and contributes to the pathogenesis of many human diseases. Although chemokines and various other chemoattractants were initially appreciated as important mediators of acute inflammation, in the past years they have emerged as critical mediators of cell migration during immune surveillance, organ development, and cancer progression. Such advances in our knowledge in chemokine biology have paved the way for the development of specific pharmacological targets with great therapeutic potential. Chemoattractants may belong to different classes, including a complex chemokine system of approximately 50 endogenous molecules that bind to G protein‐coupled receptors, which are expressed by a wide variety of cell types. Also, an unknown number of other chemoattractants may be generated by pathogens and damaged/dead cells. Therefore, blocking chemotaxis without causing side effects is an extremely challenging task. In this review, we focus on recent advances in understanding how the chemokine system orchestrates immune cell migration and positioning at the whole organ level in homeostasis, inflammation, and infection.

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“…Table 1. Chemokine receptors with their ligand pairings in humans and mice and various kinds of immune cells expressing chemokine receptors [8,[13][14][15] T N , naïve T cell; T RCM , recirculating memory T cell; T reg , regulatory T cell; and T RM , tissue-resident memory T cell. a , chemokine ligands with black, red, and blue colours represent chemokine-chemokine receptor interactions that occur in both mice and humans, only humans, and only mice, respectively.…”

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“…Cells migrating in embryogenesis (1)(2)(3), immune responses (4,5) and neural pathfinding (6,7) steer using chemotaxis, migrating up gradients of attractants such as chemokines and netrins.…”

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“…Several inflammatory mediators, including cytokines and chemokines, increase vascular permeability to facilitate sequential recruitment of immune cell types toward the site of infection [38]. Furthermore, molecules released by infectious agents are also recognized as chemoattractant signals for a number of infiltrating cells [39].…”