Canonical and atypical chemokine receptors in the neutrophil life cycle.

Chemokines are mainly studied for their local function in the control of leukocyte extravasation in homeostatic and inflammatory conditions. However, they have additional roles at the systemic level including the regulation of the hematopoietic process and leukocyte differentiation. Due to the redundancy and pleiotropicity of the chemokine system, chemokines have often multiple and complex roles in neutrophil differentiation ranging from retention and control of proliferation of progenitors to the mobilization of mature cells from the bone marrow (BM) to the bloodstream and their further differentiation in tissues. Atypical chemokine receptors (ACKRs) are regulators of the chemokine system by controlling chemokine bioavailability and chemokine receptor function. Even though ACKRs bind a wide range of chemokines, they appear to have a selective role in the process of neutrophil production and differentiation. The aim of this review is to give an overview of the current evidence regarding the role of chemokines and chemokine receptors in the life of neutrophils with a focus on the regulation exerted by ACKRs.