title: 'Emergency exit' of bone-marrow-resident CD34(+)DNAM-1(bright)CXCR4(+)-committed lymphoid precursors during chronic infection and inflammation.
abstract: During chronic inflammatory disorders, a persistent natural killer (NK) cell derangement is observed. While increased cell turnover is expected, little is known about whether and how NK-cell homeostatic balance is maintained. Here, flow cytometric analysis of peripheral blood mononuclear cells in chronic inflammatory disorders, both infectious and non-infectious, reveals the presence of a CD34(+)CD226(DNAM-1)(bright)CXCR4(+) cell population displaying transcriptional signatures typical of common lymphocyte precursors and giving rise to NK-cell progenies with high expression of activating receptors and mature function and even to α/β T lymphocytes. CD34(+)CD226(bright)CXCR4(+) cells reside in bone marrow, hardly circulate in healthy donors and are absent in cord blood. Their proportion correlates with the degree of inflammation, reflecting lymphoid cell turnover/reconstitution during chronic inflammation. These findings provide insight on intermediate stages of NK-cell development, a view of emergency recruitment of cell precursors, and upgrade our understanding and monitoring of chronic inflammatory conditions.
authors.affiliation: Department of Experimental Medicine, University of Genova, Via Pastore 1, Genova 16132, Italy.|Center for Excellence in Biomedical Research, University of Genova, Via Pastore 1, Genova 16132, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Bozzano
authors.affiliation: Istituto Giannina Gaslini, Genova 16148, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Marras
authors.affiliation: Department of Transfusion Medicine, Clinical Center and Center of Human Immunology, National Institutes of Health, Bethesda, Maryland 20892, USA.|Department of Oncology, Johns Hopkins University, Baltimore, Maryland 21231, USA.
authors.forename: Maria Libera
authors.initials: ML
authors.lastname: Ascierto
authors.affiliation: Department of Experimental Medicine, University of Genova, Via Pastore 1, Genova 16132, Italy.|Center for Excellence in Biomedical Research, University of Genova, Via Pastore 1, Genova 16132, Italy.|Istituto Giannina Gaslini, Genova 16148, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Cantoni
authors.affiliation: U.O.C. Malattie Infettive, Ospedale Galliera, Mura delle Cappuccine 14, Genova 16128, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cenderello
authors.affiliation: U.O.C. Malattie Infettive, Ospedale Sanremo, Via Privata Barabino 15, Sanremo 18038, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Dentone
authors.affiliation: Clinica Malattie Infettive, IRCCS AOU San Martino-IST Genova, Istituto Nazionale per la Ricerca sul Cancro, Largo Rosanna Benzi 10, Genova 16132, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Di Biagio
authors.affiliation: SOC Malattie Infettive ASO S.S. Antonio e Biagio e C. Arrigo Alessandria, 15100, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Orofino
authors.affiliation: U.O.C. Malattie Infettive, Ospedale Amedeo di Savoia, Torino 10149, Italy.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Mantia
authors.affiliation: U.O.C. Malattie Infettive, Ospedale Sant'Andrea, La Spezia 19121, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Boni
authors.affiliation: U.O.C. Malattie Infettive, Azienda Sanitaria Locale n.2, Savona 17100, Italy.
authors.forename: Pasqualina
authors.initials: P
authors.lastname: De Leo
authors.affiliation: Allergy and Respiratory Unit, Department of Internal Medicine, University of Genova, Via Pastore 1, Genova 16132, Italy.
authors.forename: Antonino
authors.initials: A
authors.lastname: Picciotto
authors.affiliation: Hepatology Unit, Department of Internal Medicine, University of Genova, Via Pastore 1, Genova 16132, Italy.
authors.forename: Fulvio
authors.initials: F
authors.lastname: Braido
authors.affiliation: Istituto Giannina Gaslini, Genova 16148, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Antonini
authors.affiliation: Department of Transfusion Medicine, Clinical Center and Center of Human Immunology, National Institutes of Health, Bethesda, Maryland 20892, USA.|Sidra Medical and Research Centre, Doha P.O. BOX 26999, Qatar.
authors.forename: Ena
authors.initials: E
authors.lastname: Wang
authors.affiliation: Sidra Medical and Research Centre, Doha P.O. BOX 26999, Qatar.
authors.forename: Francesco
authors.identifier: http://orcid.org/0000-0001-6423-391X
authors.initials: F
authors.lastname: Marincola
authors.affiliation: Istituto Giannina Gaslini, Genova 16148, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moretta
authors.affiliation: Center for Excellence in Biomedical Research, University of Genova, Via Pastore 1, Genova 16132, Italy.|Clinica Malattie Infettive, IRCCS AOU San Martino-IST Genova, Istituto Nazionale per la Ricerca sul Cancro, Largo Rosanna Benzi 10, Genova 16132, Italy.|Department of Health Sciences, DISSAL, University of Genova, Via Pastore 1, Genova 16132, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: De Maria
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D001853:Bone Marrow / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D016022:Case-Control Studies; D005312:Fetal Blood / Q000166:cytology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000235:genetics / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D054503:Lymphoid Progenitor Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics / Q000276:immunology*; D019718:Receptors, CXCR4 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014397:Tuberculosis, Pulmonary / Q000235:genetics / Q000276:immunology*; D000098862:T Lineage-Specific Activation Antigen 1
chemical_list: D018952:Antigens, CD34; D000945:Antigens, Differentiation, T-Lymphocyte; D000098862:T Lineage-Specific Activation Antigen 1; C527276:CXCR4 protein, human; D019718:Receptors, CXCR4