Recent findings have uncovered novel fascinating aspects of the biology of neutrophils, which ultimately attribute to these cells a broader role in inflammation and immunity. One aspect that is currently under intensive investigation is the notion of neutrophil ‘heterogeneity’. Studies examining neutrophils in a variety of acute and chronic inflammatory conditions report, in fact, the recovery of CD66b+ cells displaying neutrophil-like morphology and able to exert either immunosuppressive or proinflammatory properties (1-4). However, due to the lack of specific markers, the precise phenotype and maturation status of these neutrophil populations remain unclear. Some of these neutrophil populations sediment within the peripheral blood mononuclear cell (PBMC) fraction after density gradient centrifugation of blood, and are thus generally defined as ‘low density neutrophils’ (LDNs) (1,3-4). The various LDN populations to date identified and described in pathological settings are heterogeneously composed by mixed populations of activated mature neutrophils, as well as neutrophils at different stages of differentiation (1,3-4). In this context, in a recent study, we demonstrated that in healthy volunteers receiving G-CSF for stem cell mobilization (GDs) mature neutrophils can be clearly distinguished from immature neutrophil populations, and, in turn, isolated from the blood, based on their selective expression of CD10 (5). By doing so, we have shown that mature CD10+ LDNs, as well as CD10+ normal dnsity neutrophil (NDNs), from GDs inhibit proliferation and IFNγ production by T cells via a CD18-mediated contact-dependent release of arginase 1(ARG1). By contrast, we have shown that immature CD66b+CD10- LDNs from GDs manifest an opposite behavior, since they promoted T cell survival and enhanced proliferation and IFNγ production by T cells via CD18-mediated contact-dependent mechanisms.Our findings uncover CD10 as a phenotypic marker discriminating mature neutrophils from immature neutrophil populations present in patients with acute or chronic inflammatory conditions, as well as facilitating their isolation, to better define their specific immunoregulatory properties.

NEUTROPHILS IN THE SAGA OF MYELOID CELL PLASTICITY

Scapini
2017-01-01

Abstract

Recent findings have uncovered novel fascinating aspects of the biology of neutrophils, which ultimately attribute to these cells a broader role in inflammation and immunity. One aspect that is currently under intensive investigation is the notion of neutrophil ‘heterogeneity’. Studies examining neutrophils in a variety of acute and chronic inflammatory conditions report, in fact, the recovery of CD66b+ cells displaying neutrophil-like morphology and able to exert either immunosuppressive or proinflammatory properties (1-4). However, due to the lack of specific markers, the precise phenotype and maturation status of these neutrophil populations remain unclear. Some of these neutrophil populations sediment within the peripheral blood mononuclear cell (PBMC) fraction after density gradient centrifugation of blood, and are thus generally defined as ‘low density neutrophils’ (LDNs) (1,3-4). The various LDN populations to date identified and described in pathological settings are heterogeneously composed by mixed populations of activated mature neutrophils, as well as neutrophils at different stages of differentiation (1,3-4). In this context, in a recent study, we demonstrated that in healthy volunteers receiving G-CSF for stem cell mobilization (GDs) mature neutrophils can be clearly distinguished from immature neutrophil populations, and, in turn, isolated from the blood, based on their selective expression of CD10 (5). By doing so, we have shown that mature CD10+ LDNs, as well as CD10+ normal dnsity neutrophil (NDNs), from GDs inhibit proliferation and IFNγ production by T cells via a CD18-mediated contact-dependent release of arginase 1(ARG1). By contrast, we have shown that immature CD66b+CD10- LDNs from GDs manifest an opposite behavior, since they promoted T cell survival and enhanced proliferation and IFNγ production by T cells via CD18-mediated contact-dependent mechanisms.Our findings uncover CD10 as a phenotypic marker discriminating mature neutrophils from immature neutrophil populations present in patients with acute or chronic inflammatory conditions, as well as facilitating their isolation, to better define their specific immunoregulatory properties.
2017
Neutrophils, Inflammation, Heterogeneity, LDNs, Immunoregulation.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/972736
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