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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 University–Hadassah 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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