‘Emergency exit’ of bone-marrow-resident CD34+DNAM-1brightCXCR4+-committed lymphoid precursors during chronic infection and inflammation

Federica Bozzano, Francesco Marras, Maria Libera Ascierto, Claudia Cantoni, Giovanni Cenderello, Chiara Dentone, Antonio Di Biagio, Giancarlo Orofino, Eugenio Mantia, Silvia Boni, Pasqualina De Leo, Antonino Picciotto, Fulvio Braido, Francesca Antonini, Ena Wang, Francesco Marincola, Lorenzo Moretta and Andrea De Maria ()
Additional contact information
Federica Bozzano: University of Genova
Francesco Marras: Istituto Giannina Gaslini
Maria Libera Ascierto: Clinical Center and Center of Human Immunology, National Institutes of Health
Claudia Cantoni: University of Genova
Giovanni Cenderello: U.O.C. Malattie Infettive, Ospedale Galliera
Chiara Dentone: U.O.C. Malattie Infettive, Ospedale Sanremo
Antonio Di Biagio: Clinica Malattie Infettive, IRCCS AOU San Martino-IST Genova, Istituto Nazionale per la Ricerca sul Cancro
Giancarlo Orofino: SOC Malattie Infettive ASO S.S. Antonio e Biagio e C. Arrigo Alessandria
Eugenio Mantia: U.O.C. Malattie Infettive, Ospedale Amedeo di Savoia
Silvia Boni: U.O.C. Malattie Infettive, Ospedale Sant’Andrea
Pasqualina De Leo: U.O.C. Malattie Infettive, Azienda Sanitaria Locale n.2
Antonino Picciotto: Allergy and Respiratory Unit, University of Genova
Fulvio Braido: Hepatology Unit, University of Genova
Francesca Antonini: Istituto Giannina Gaslini
Ena Wang: Clinical Center and Center of Human Immunology, National Institutes of Health
Francesco Marincola: Sidra Medical and Research Centre
Lorenzo Moretta: Istituto Giannina Gaslini
Andrea De Maria: Center for Excellence in Biomedical Research, University of Genova

Nature Communications, 2015, vol. 6, issue 1, 1-14

Abstract: 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)brightCXCR4+ 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+CD226brightCXCR4+ 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.

Date: 2015
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DOI: 10.1038/ncomms9109

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