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 chem...

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Bibliographic Details
Published in:Blood 2003-09, Vol.102 (5), p.1569-1577
Main Authors: Hanna, Jacob, Wald, Ori, Goldman-Wohl, Debra, Prus, Diana, Markel, Gal, Gazit, Roi, Katz, Gil, Haimov-Kochman, Ronit, Fujii, Nobutaka, Yagel, Simcha, Peled, Amnon, Mandelboim, Ofer
Format: Article
Language:English
Subjects:
Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
Biological and medical sciences
Blood Vessels - cytology
Bone marrow, stem cells transplantation. Graft versus host reaction
Cell Movement - immunology
Chemokine CXCL10
Chemokine CXCL12
Chemokine CXCL9
Chemokines, CXC - genetics
Chemokines, CXC - immunology
Chemokines, CXC - metabolism
Decidua - blood supply
Decidua - cytology
Decidua - immunology
Female
Gene Expression - immunology
Hematologic and hematopoietic diseases
Humans
Intercellular Signaling Peptides and Proteins - genetics
Intercellular Signaling Peptides and Proteins - metabolism
Killer Cells, Natural - chemistry
Killer Cells, Natural - cytology
Killer Cells, Natural - immunology
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Ligands
Medical sciences
Pregnancy
Receptors, Cell Surface - genetics
Receptors, Cell Surface - metabolism
Receptors, Chemokine - genetics
Receptors, Chemokine - metabolism
Receptors, CXCR3
Receptors, CXCR4 - genetics
Receptors, CXCR4 - metabolism
Receptors, IgG - analysis
RNA, Messenger - analysis
Transfusions. Complications. Transfusion reactions. Cell and gene therapy
Trophoblasts - cytology
Trophoblasts - immunology
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Summary: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.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2003-02-0517