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Early studies on chemokine receptors suggested that these receptors could regulate different cellular functions and not only chemotaxis. However, due to the key importance of chemotaxis in biology, analysis of alternative functions that chemokine receptors could regulate in leukocytes have been neglected ...

Early studies on chemokine receptors suggested that these receptors could regulate different cellular functions and not only chemotaxis. However, due to the key importance of chemotaxis in biology, analysis of alternative functions that chemokine receptors could regulate in leukocytes have been neglected during the last years. The data available, although sparse, clearly gives support to the early concept that chemokine receptors are multifunctional. For example, recent studies have demonstrated that the chemokine receptor CCR7 can control the chemotaxis, survival, migratory speed, cytoarchitecture, endocytosis and differentiation of mature dendritic cells. CXCR2 is known to control the chemotaxis, phagocytosis, exocytosis, cytoarchitecture, respiratory burst and the adhesion of neutrophils. In addition, CXCR2 has been shown to regulate respiratory burst, neutrophil extracellular traps (NET) formation, degranulation, integrin activation leading to arrest, chemokinesis and actin polymerization. Taken together, these studies indicate that the sum of biological activities governed by a given chemokine receptor in a specific leukocyte contribute to its ability to mount more efficient immune responses under homeostasis and during inflammation in response to insults such as infection and tissue damage.

Gaining insight into the cellular activities controlled by chemokine receptors in leukocytes as well as the signaling pathways driving these functions can be useful to develop strategies to modulate the immune response.

In this Research Topic, we aim to discuss the range of functions orchestrated by chemokine receptors and other non-chemokine chemoattractant receptors of leukocytes, beyond chemotaxis, including their roles in:

(i) Immune cell metabolism.
(ii) Immune cell differentiation.
(iii) Immune cell polarization.
(iv) Immune cell survival.
(v) Cancer.

In this way, we aim to uncover novel targets and signaling pathways that could be exploited for modulating immune responses under normal conditions and in disease.

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