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 alpha(4) integrin plays a pivotal role in the maintenance of NK cells in the BM sinusoids and that alpha(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-gamma 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. (Blood. 2011; 117(17): 4467-4475)

CX3CR1 expression defines 2 KLRG1+ mouse NK-cell subsets with distinct functional properties and positioning in the bone marrow / Sciume', Giuseppe; G., De Angelis; Benigni, Giorgia; Ponzetta, Andrea; Morrone, Stefania; Santoni, Angela; Bernardini, Giovanni. - In: BLOOD. - ISSN 0006-4971. - STAMPA. - 117:17(2011), pp. 4467-4475. [10.1182/blood-2010-07-297101]

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

SCIUME', GIUSEPPE;BENIGNI, GIORGIA;PONZETTA, ANDREA;MORRONE, Stefania;SANTONI, Angela;BERNARDINI, Giovanni
2011

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(+) 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 alpha(4) integrin plays a pivotal role in the maintenance of NK cells in the BM sinusoids and that alpha(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-gamma 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. (Blood. 2011; 117(17): 4467-4475)
2011
01 Pubblicazione su rivista::01a Articolo in rivista
CX3CR1 expression defines 2 KLRG1+ mouse NK-cell subsets with distinct functional properties and positioning in the bone marrow / Sciume', Giuseppe; G., De Angelis; Benigni, Giorgia; Ponzetta, Andrea; Morrone, Stefania; Santoni, Angela; Bernardini, Giovanni. - In: BLOOD. - ISSN 0006-4971. - STAMPA. - 117:17(2011), pp. 4467-4475. [10.1182/blood-2010-07-297101]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/380812
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