CXCL12 expression by invasive trophoblasts induces the specific migration of CD16– human natural killer cells

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

doi:10.1182/blood-2003-02-0517

Cited by 314 publications

(292 citation statements)

References 52 publications

Supporting

Mentioning

266

Contrasting

Unclassified

Order By: Relevance

“…In correlation with these observations, CD56 bright CD16 Ϫ cells have been shown as important players in regulating and priming immune responses via cytokine-mediated cross-talk with neighboring dendritic (DC) and T cells (6,10). In contrast, the more cytotoxic subset, CD56 dim CD16 ϩ , has higher levels of CXCR1 and CX3CR1 chemokine receptors (7,8), and therefore is preferentially recruited to sites of inflammation (4). Signals transduced by locally secreted inflammatory cytokines and specific encounters with target cells synergize to induce activation of this subset.…”

mentioning

confidence: 69%

“…7). One explanation for the activated-like phenotype of the decidual NK subset can be inferred from the chronic intimate interaction of these cells with semiallogeneic extravillous trophoblasts that invade maternal decidua and the cytokine-enriched local microenvironment (7,64). Such conditions might induce, at least, a partial activation state on NK cells found in the decidua.…”

Section: Discussionmentioning

confidence: 99%

“…The majority of pbNK cells (Ͼ90%) are phenotypically characterized as CD56 dim CD16 ϩ , while the remaining cells are CD56 bright CD16 Ϫ (4). The fact that each of these subsets expresses a unique repertoire of chemokine receptors and adhesion molecules encouraged several groups to characterize the NK cell pool in secondary lymphoid tissues and inflammation sites (5)(6)(7).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Novel Insights on Human NK Cells’ Immunological Modalities Revealed by Gene Expression Profiling

Hanna¹,

Bechtel

Zhai

et al. 2004

The Journal of Immunology

Self Cite

143

147

View full text Add to dashboard Cite

As part of the innate immune system, human NK cells play a critical role early in the systemic host defense against pathogens and tumor cells. Recent studies suggest a more complex view of NK cell behavior, as different functions and tissue localizing capabilities seem to be preferentially assigned to distinct subpopulations of NK cells, CD56dimCD16+ or CD56brightCD16−. In this study, we used oligonucleotide microarrays to compare the expression profile of ∼20,000 genes in three NK cell subpopulations: peripheral blood-derived CD56dimCD16+, CD56brightCD16−, and in vitro-activated CD16+ NK cells. The differential expression of selected genes was verified by flow cytometry and functional assays. When comparing CD56dimCD16+ and CD56brightCD16− subsets, a new heterogeneous molecular basis for the functional and developmental differences between these two subsets was revealed. Furthermore, systematic analysis of transcriptional changes in activated CD16+ NK cells provided us with a better understanding of NK function in inflamed tissues. We highlight a number of genes that were overexpressed upon activation (e.g., OX40 ligand, CD86, Tim3, galectins, etc.), that enable these cells to directly cross-talk with other innate and adaptive immune effectors. The overexpressed genes assign novel intriguing immunomodulatory functions to activated NK cells, in addition to their potent cytotoxic abilities.

show abstract

mentioning

confidence: 69%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Novel Insights on Human NK Cells’ Immunological Modalities Revealed by Gene Expression Profiling

Hanna¹,

Bechtel

Zhai

et al. 2004

The Journal of Immunology

Self Cite

143

147

View full text Add to dashboard Cite

show abstract

“…CXCR4 has been previously implicated in migration and activation of MDSCs in cancer (40,41). CXCL12, the ligand for CXCR4, has been shown to be expressed by trophoblast and decidual stromal cells and to be responsible for homing of decidual NK cells (42,43). Recently, Zhao et al (37) showed an association of an upregulation of CXCL12 and an accumulation of MDSCs in the pregnant mouse uterus.…”

Section: Discussionmentioning

confidence: 99%

Granulocytic Myeloid-Derived Suppressor Cells Accumulate in Human Placenta and Polarize toward a Th2 Phenotype

Köstlin

Hofstädter

Ostermeir

et al. 2016

The Journal of Immunology

101

View full text Add to dashboard Cite

Tolerance induction toward the semiallogeneic fetus is crucial to enable a successful pregnancy; its failure is associated with abortion or preterm delivery. Skewing T cell differentiation toward a Th2-dominated phenotype seems to be pivotal in maternal immune adaption, yet underlying mechanisms are incompletely understood. Myeloid-derived suppressor cells (MDSCs) are innate immune cells that mediate T cell suppression and are increased in cord blood of healthy newborns and in peripheral blood of pregnant women. In this study, we demonstrate that granulocytic MDSCs (GR-MDSCs) accumulate in human placenta of healthy pregnancies but are diminished in patients with spontaneous abortions. Placental GR-MDSCs effectively suppressed T cell responses by expression of arginase I and production of reactive oxygen species and were activated at the maternal–fetal interface through interaction with trophoblast cells. Furthermore, GR-MDSCs isolated from placenta polarized CD4+ T cells toward a Th2 cytokine response. These results highlight a potential role of GR-MDSCs in inducing and maintaining maternal–fetal tolerance and suggest them as a promising target for therapeutic manipulation of pregnancy complications.

show abstract

“…Indirect evidence suggests that CD56 bright CD16 2 dNK cells originate from CD56 bright CD16 2 pNK cells. 37,38 In this study, our results showed that trophoblasts had no effect on the expression of cell surface molecules or intracellular cytokines by CD56 bright pNK cells, also suggested the resemblance of peripheral CD56 bright NK cells to dNK cells (Supplementary Figure 2). Our previous studies demonstrated that at the maternal/fetal interface, CXCL12 was mainly produced by trophoblasts and to a lesser extent by decidual stromal cells, while CXCR4 was intermediately expressed on dNK cells and highly expressed on peripheral NK cells (Ref.…”

Section: Discussionmentioning

confidence: 69%

CD56brightCD25+ NK cells are preferentially recruited to the maternal/fetal interface in early human pregnancy

Piao

et al. 2014

Cell Mol Immunol

View full text Add to dashboard Cite

Decidual natural killer (dNK) cells are believed to be critical for maintaining maternal/fetal tolerance and regulating placental vascular remodeling based upon their abundance and unique phenotype during early pregnancy. However, the mechanism for how the dNK cells play such important roles in successful pregnancy remains undefined. Here, we identified a subtype of dNK cells characterized as having a CD3 2 CD56 bright CD25 1 phenotype. We found that CD56 bright CD25 1 NK cells preferentially localize to the maternal/fetal interface during early human pregnancy. CD25 1 dNK cells account for approximately 75% of CD25-expressing decidual immune cells (DICs). However, less than 5% of CD25-positive peripheral blood mononuclear cells are CD25 1 NK cells. Furthermore, CD25 1 and CD25 2 dNK cells exhibit distinct phenotypes: CD25 1 dNK cells display a more activated phenotype and greater cytokine-secreting capacity. Interestingly, coculture of peripheral NK (pNK) cells with primary trophoblasts upregulates the percentage of CD25-expressing pNK cells, resulting in increased expression of activation markers and cytokine production by pNK cells. In addition, we demonstrated that the CXCL12/CXCR4 axis is crucial for the recruitment of CD25 1 dNK cells and contributes to the accumulation of CD3 2 CD56 bright CD25 1 dNK cells at the maternal/fetal interface. Thus, our data reveal that the crosstalk between trophoblasts and pNK cells leads to the accumulation of CD3 2 CD56 bright CD25 1 dNK cells, which exert a regulating effect at the maternal/fetal interface.

show abstract

CXCL12 expression by invasive trophoblasts induces the specific migration of CD16– human natural killer cells

Cited by 314 publications

References 52 publications

Novel Insights on Human NK Cells’ Immunological Modalities Revealed by Gene Expression Profiling

Novel Insights on Human NK Cells’ Immunological Modalities Revealed by Gene Expression Profiling

Granulocytic Myeloid-Derived Suppressor Cells Accumulate in Human Placenta and Polarize toward a Th2 Phenotype

CD56brightCD25+ NK cells are preferentially recruited to the maternal/fetal interface in early human pregnancy

Contact Info

Product

Resources

About