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

Chemotaxis 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.