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Prepublished online as a Blood First Edition Paper on May 1, 2003; DOI 10.1182/blood-2003-02-0517.
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Blood, 1 September 2003, Vol. 102, No. 5, pp. 1569-1577
CHEMOKINES
CXCL12 expression by invasive trophoblasts induces the specific migration of CD16 human natural killer cells
Jacob Hanna,
Ori Wald,
Debra Goldman-Wohl,
Diana Prus,
Gal Markel,
Roi Gazit,
Gil Katz,
Ronit Haimov-Kochman,
Nobutaka Fujii,
Simcha Yagel,
Amnon Peled, and
Ofer Mandelboim
From The Lautenberg Center for General and Tumor Immunology, Hebrew
UniversityHadassah Medical School, Jerusalem, Israel; Goldyne Savad
Institute of Gene Therapy, Hadassah University Hospital, Jerusalem, Israel;
Department of Obstetrics and Gynecology, Hadassah University Hospital-Mount
Scopus, Jerusalem, Israel; Department of Pathology, Hadassah University
Hospital-Mount Scopus, Jerusalem, Israel; Graduate School of Pharmaceutical
Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan.
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.

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