CX3CR1 expression defines 2 KLRG1+ mouse NK-cell subsets with distinct functional properties and positioning in the bone marrow

Giuseppe Sciumè, Giulia De Angelis, Giorgia Benigni, Andrea Ponzetta, Stefania Morrone, Angela Santoni, Giovanni Bernardini

Research output: Contribution to journalArticle

Abstract

During development in the bone marrow (BM), NK-cell positioning within specific niches can be influenced by expression of chemokine or adhesion receptors. We previously demonstrated that the maintenance in the BM of selected NK-cell subsets is regulated by the CXCR4/CXCL12 axis. In the present study, we showed that CX3CR1 is prevalently expressed on KLRG1+ NK cells, a subset considered terminally differentiated. Two KLRG1- NKcell populations endowed with distinct homing and functional features were defined according to CX3CR1 expression. In the BM, KLRG1+/CX3CR1- NK cells were mainly positioned into parenchyma, while KLRG1+/ CX3CR1+ NK cells exhibited reduced CXCR4 expression and were preferentially localized in the sinusoids. We also showed that α4 integrin plays a pivotal role in the maintenance of NK cells in the BM sinusoids and that α4 neutralization leads to strong reduction of BM KLRG1+/CX3CR1+ NK cells. Moreover, we found that KLRG1+/CX3CR1+ cells originate from KLRG1 +/CX3CR1- NK-cell population and display impaired capability to produce IFN-γ and to lyse YAC-1 target cells on cytokine stimulation. Altogether, our findings show that CX3CR1 represents a marker of a KLRG1+ NK-cell population with unique properties that can irreversibly differentiate from the KLRG1+/CX3CR1- NK cells during steady state conditions.

Original languageEnglish
Pages (from-to)4467-4475
Number of pages9
JournalBlood
Volume117
Issue number17
DOIs
Publication statusPublished - Apr 28 2011

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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    Sciumè, G., De Angelis, G., Benigni, G., Ponzetta, A., Morrone, S., Santoni, A., & Bernardini, G. (2011). CX3CR1 expression defines 2 KLRG1+ mouse NK-cell subsets with distinct functional properties and positioning in the bone marrow. Blood, 117(17), 4467-4475. https://doi.org/10.1182/blood-2010-07-297101