title: CX3CR1 expression defines 2 KLRG1+ mouse NK-cell subsets with distinct functional properties and positioning in the bone marrow.
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 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.
authors.affiliation: Department of Molecular Medicine-Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome, Italy. giovanni.bernardini@uniroma1.it
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Sciumè
authors.forename: Giulia
authors.initials: G
authors.lastname: De Angelis
authors.forename: Giorgia
authors.initials: G
authors.lastname: Benigni
authors.forename: Andrea
authors.initials: A
authors.lastname: Ponzetta
authors.forename: Stefania
authors.initials: S
authors.lastname: Morrone
authors.forename: Angela
authors.initials: A
authors.lastname: Santoni
authors.forename: Giovanni
authors.initials: G
authors.lastname: Bernardini
mesh_terms: D000818:Animals; D015415:Biomarkers; D001854:Bone Marrow Cells / Q000145:classification / Q000166:cytology / Q000502:physiology*; D000073883:CX3C Chemokine Receptor 1; D002454:Cell Differentiation / Q000276:immunology; D054377:Chemokine CXCL12 / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression / Q000276:immunology; D049452:Green Fluorescent Proteins / Q000235:genetics; D039441:Integrin alpha4 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000145:classification / Q000166:cytology / Q000502:physiology*; D037181:Lectins, C-Type; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics* / Q000276:immunology / Q000378:metabolism
chemical_list: D015415:Biomarkers; D000073883:CX3C Chemokine Receptor 1; C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; C471885:Cx3cr1 protein, mouse; C515256:Cxcl12 protein, mouse; C451496:Klrg1 protein, mouse; D037181:Lectins, C-Type; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine; D011971:Receptors, Immunologic; D039441:Integrin alpha4; D049452:Green Fluorescent Proteins