CXCL12 expression by invasive trophoblasts induces the specific migration of CD16- human natural killer cells.
In the maternal decidua, natural killer (NK) cells, characterized by lack of CD16, are found in direct contact with the fetal extravillous trophoblasts (EVTs). It is yet unknown which factors contribute to the specific homing of this unique NK subset to the decidua. In this study we analyze the chemokine receptor repertoire on various NK populations derived from the peripheral blood and decidua. We show that CXCR4 and CXCR3 receptors are preferentially expressed on CD16- NK subsets derived either from the peripheral blood or the decidua and that these receptors are involved in migration of all NK subsets to their ligands. We further demonstrate in vivo that invading EVTs that eventually perform endovascular invasion express CXCL12, the ligand for CXCR4, but not ligands for CXCR3. Indeed, specific accumulation of the CD16- NK cells at the expense of CD16+ cells was observed only when in vitro migration was performed with ligands for CXCR4. Finally, incubation of the peripheral blood CD16- NK cells with cytokines present in the decidua, especially interleukin 15 (IL-15), resulted in the expression of chemokine receptor repertoire similar to that observed on decidual NK cells, suggesting an additional important regulatory effect of local decidual cytokines.
The Lautenberg Center for General and Tumor Immunology, Hebrew University-Hadassah Medical School, Jerusalem, 91120, Israel. oferman@md2.huji.ac.il
Jacob
J
Hanna
Ori
O
Wald
Debra
D
Goldman-Wohl
Diana
D
Prus
Gal
G
Markel
Roi
R
Gazit
Gil
G
Katz
Ronit
R
Haimov-Kochman
Nobutaka
N
Fujii
Simcha
S
Yagel
Amnon
A
Peled
Ofer
O
Mandelboim
D001808:Blood Vessels / Q000166:cytology; D002465:Cell Movement / Q000276:immunology*; D054357:Chemokine CXCL10; D054377:Chemokine CXCL12; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D003656:Decidua / Q000098:blood supply / Q000166:cytology / Q000276:immunology*; D005260:Female; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D007694:Killer Cells, Natural / Q000737:chemistry / Q000166:cytology* / Q000276:immunology; D008024:Ligands; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D054367:Receptors, CXCR3; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D017452:Receptors, IgG / Q000032:analysis; D014327:Trophoblasts / Q000166:cytology / Q000276:immunology*
C515255:CXCL12 protein, human; C080810:CXCL9 protein, human; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D054377:Chemokine CXCL12; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D012333:RNA, Messenger; D054367:Receptors, CXCR3; D019718:Receptors, CXCR4; D011956:Receptors, Cell Surface; D019707:Receptors, Chemokine; D017452:Receptors, IgG