title: Mature CD10+and immature CD10-neutrophils present in G-CSF-treated donors display opposite effects on T cells.
abstract: The identification of discrete neutrophil populations, as well as the characterization of their immunoregulatory properties, is an emerging topic under extensive investigation. In such regard, the presence of circulating CD66b+neutrophil populations, exerting either immunosuppressive or proinflammatory functions, has been described in several acute and chronic inflammatory conditions. However, due to the lack of specific markers, the precise phenotype and maturation status of these neutrophil populations remain unclear. Herein, we report that CD10, also known as common acute lymphoblastic leukemia antigen, neutral endopeptidase, or enkephalinase, can be used as a marker that, within heterogeneous populations of circulating CD66b+neutrophils present in inflammatory conditions, clearly distinguishes the mature from the immature ones. Accordingly, we observed that the previously described immunosuppressive neutrophil population that appears in the circulation of granulocyte colony-stimulating factor (G-CSF)-treated donors (GDs) consists of mature CD66b+CD10+neutrophils displaying an activated phenotype. These neutrophils inhibit proliferation and interferon γ (IFNγ) production by T cells via a CD18-mediated contact-dependent arginase 1 release. By contrast, we found that immature CD66b+CD10-neutrophils, also present in GDs, display an immature morphology, promote T-cell survival, and enhance proliferation and IFNγ production by T cells. Altogether, our findings uncover that in GDs, circulating mature and immature neutrophils, distinguished by their differential CD10 expression, exert opposite immunoregulatory properties. Therefore, CD10 might be used 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.
authors.affiliation: Division of General Pathology.
authors.forename: Olivia
authors.initials: O
authors.lastname: Marini
authors.affiliation: Division of General Pathology.
authors.forename: Sara
authors.initials: S
authors.lastname: Costa
authors.affiliation: Division of General Pathology.
authors.forename: Dalila
authors.initials: D
authors.lastname: Bevilacqua
authors.affiliation: Division of General Pathology.
authors.forename: Federica
authors.initials: F
authors.lastname: Calzetti
authors.affiliation: Division of General Pathology.
authors.forename: Nicola
authors.initials: N
authors.lastname: Tamassia
authors.affiliation: Division of Hematology and Bone Marrow Transplant Unit.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Spina
authors.affiliation: Division of Hematology and Bone Marrow Transplant Unit.
authors.forename: Donata
authors.initials: D
authors.lastname: De Sabata
authors.affiliation: Division of Internal Medicine, Department of Medicine.
authors.forename: Elisa
authors.initials: E
authors.lastname: Tinazzi
authors.affiliation: Division of Internal Medicine, Department of Medicine.
authors.forename: Claudio
authors.initials: C
authors.lastname: Lunardi
authors.affiliation: Interdepartmental Laboratory of Medical Research, and.
authors.forename: Maria T
authors.initials: MT
authors.lastname: Scupoli
authors.affiliation: Interdepartmental Laboratory of Medical Research, and.
authors.forename: Chiara
authors.initials: C
authors.lastname: Cavallini
authors.affiliation: Applied Research on Cancer-Network, University of Verona, Verona, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Zoratti
authors.affiliation: Rheumatology Unit, Division of General Medicine, Sacro Cuore Hospital of Negrar, Verona, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Tinazzi
authors.affiliation: Rheumatology Unit, Division of General Medicine, Sacro Cuore Hospital of Negrar, Verona, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Marchetta
authors.affiliation: Transfusion Medicine Department, Integrated University Hospital, Verona, Italy.
authors.forename: Aurora
authors.initials: A
authors.lastname: Vassanelli
authors.affiliation: Transfusion Medicine Department, Integrated University Hospital, Verona, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Cantini
authors.affiliation: Transfusion Medicine Department, Integrated University Hospital, Verona, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Gandini
authors.affiliation: Department of Surgery, Division of General Surgery "A," University of Verona, Verona, Italy; and.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ruzzenente
authors.affiliation: Department of Surgery, Division of General Surgery "A," University of Verona, Verona, Italy; and.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Guglielmi
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Missale
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: William
authors.initials: W
authors.lastname: Vermi
authors.affiliation: Division of Hematology and Bone Marrow Transplant Unit.
authors.forename: Cristina
authors.initials: C
authors.lastname: Tecchio
authors.affiliation: Division of General Pathology.
authors.forename: Marco A
authors.initials: MA
authors.lastname: Cassatella
authors.affiliation: Division of General Pathology.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Scapini
mesh_terms: D015415:Biomarkers / Q000032:analysis*; D002469:Cell Separation; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D015260:Neprilysin / Q000032:analysis / Q000096:biosynthesis* / Q000276:immunology; D009504:Neutrophils / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D015415:Biomarkers; D016179:Granulocyte Colony-Stimulating Factor; D015260:Neprilysin