'Emergency exit' of bone-marrow-resident CD34+ DNAM-1 bright CXCR4+-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, Andrea De Maria

Research output: Contribution to journalArticle

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+ CD226bright 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.

Original languageEnglish
Article number8109
JournalNature Communications
Volume6
DOIs
Publication statusPublished - Oct 5 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

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    Bozzano, F., Marras, F., Ascierto, M. L., Cantoni, C., Cenderello, G., Dentone, C., Di Biagio, A., Orofino, G., Mantia, E., Boni, S., De Leo, P., Picciotto, A., Braido, F., Antonini, F., Wang, E., Marincola, F., Moretta, L., & De Maria, A. (2015). 'Emergency exit' of bone-marrow-resident CD34+ DNAM-1 bright CXCR4+-committed lymphoid precursors during chronic infection and inflammation. Nature Communications, 6, [8109]. https://doi.org/10.1038/ncomms9109