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

Giuseppe Sciumè (1) , Giulia de Angelis (1) , Giorgia Benigni (1) , Andrea Ponzetta (1) , Stefania Morrone (1) , Angela Santoni (1, 2) , Giovanni Bernardini (1)

1 Department of Molecular Medicine
2 NEUROMED I.R.C.C.S. - Istituto Neurologico Mediterraneo

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(+) NK-cell 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 α(4) integrin plays a pivotal role in the maintenance of NK cells in the BM sinusoids and that α(4) 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.

Domaines: Immunologie

Giuseppe Sciumè, Giulia de Angelis, Giorgia Benigni, Andrea Ponzetta, Stefania Morrone, et al.. CX3CR1 expression defines 2 KLRG1+ mouse NK-cell subsets with distinct functional properties and positioning in the bone marrow.. Blood, 2011, 117 (17), pp.4467-75. ⟨10.1182/blood-2010-07-297101⟩. ⟨pasteur-00942620⟩