The CXCL12/CXCR4 axis is involved in the maintenance of Th2 bias at the maternal/fetal interface in early human pregnancy

Piao, Hailan; Yu, Tao; Zhu, Rui; Wang, Songcun; Tang, Chuan-Ling; Fu, Qiang; Du, Meirong; Li, Da‐Jin

doi:10.1038/cmi.2012.23

Cited by 53 publications

(42 citation statements)

References 35 publications

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“…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

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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.

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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

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“…1,2 Recent data from both mice and humans have demonstrated that the maternal/fetal interface exhibits a T H 2 bias during pregnancy. 3 A failure to establish such an immune milieu or exhibiting a T H 1 bias, such as the overexpression of interferon (IFN)-c or tumor-necrosis factora, is associated with recurrent spontaneous abortion in humans. 4,5 It also has been proven that regulatory T (Treg) cells increase during the first and second trimesters and peak in the second trimester in human decidua and peripheral blood.…”

Section: Introductionmentioning

confidence: 99%

Decidual stromal cells recruit Th17 cells into decidua to promote proliferation and invasion of human trophoblast cells by secreting IL-17

Jin

et al. 2014

Cell Mol Immunol

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T helper 17 (Th17) cells have both regulatory and protective roles in physiological conditions. The Th17 subset and the cytokine interleukin-17A (IL-17A) have been implicated in the pathogenesis of certain autoimmune diseases, several types of cancer and allograft rejection. However, the role of Th17 cells at the maternal/fetal interface remains unknown. Here, we demonstrate that Th17 cells are present in decidua and are increased in the peripheral blood of 10 clinically normal pregnancies based on intracellular cytokine analysis. Our results suggest a potential role of Th17 cells in sustaining pregnancy in humans. Furthermore, we demonstrate that decidual stromal cells (DSCs) but not trophoblast cells recruit peripheral Th17 cells into the decidua by secreting CCL2. The recruited Th17 cells promote proliferation and invasion and inhibit the apoptosis of human trophoblast cells by secreting IL-17 during the first trimester of pregnancy. These findings indicate a novel role for Th17 cells in controlling the maternal-fetal relationship and placenta development.

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“…Furthermore, CXCL12 produced by trophoblast also contributes to Th2 bias at the maternal-fetal interface. 82 Although the exact mechanism is not known, CXCL12 may associate with signal transducers and activator of transcription-6. 83, 84 Huang and Fan reported that cdT cells recruited into the decidua via CXCL16/CXCR6 interaction play an important role in the Th2 bias at the maternal-fetal interface and in the development and progression of the placenta by producing high levels of IL-10 and TGF-b.…”

mentioning

confidence: 99%

“…82 Although the exact mechanism is not known, CXCL12 may associate with signal transducers and activator of transcription-6. 83, 84 Huang and Fan reported that cdT cells recruited into the decidua via CXCL16/CXCR6 interaction play an important role in the Th2 bias at the maternal-fetal interface and in the development and progression of the placenta by producing high levels of IL-10 and TGF-b. 32,85 Therefore, trophoblasts and DSCs appear to induce the differentiation of immune cells into an embryo-supporting phenotype.…”

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confidence: 99%

The integrative roles of chemokines at the maternal–fetal interface in early pregnancy

2014

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Embryos express paternal antigens that are foreign to the mother, but the mother provides a special immune milieu at the fetal-maternal interface to permit rather than reject the embryo growth in the uterus until parturition by establishing precise crosstalk between the mother and the fetus. There are unanswered questions in the maintenance of pregnancy, including the poorly understood phenomenon of maternal tolerance to the allogeneic conceptus, and the remarkable biological roles of placental trophoblasts that invade the uterine wall. Chemokines are multifunctional molecules initially described as having a role in leukocyte trafficking and later found to participate in developmental processes such as differentiation and directed migration. It is increasingly evident that the gestational uterine microenvironment is characterized, at least in part, by the differential expression and secretion of chemokines that induce selective trafficking of leukocyte subsets to the maternal-fetal interface and regulate multiple events that are closely associated with normal pregnancy. Here, we review the expression and function of chemokines and their receptors at the maternal-fetal interface, with a special focus on chemokine as a key component in trophoblast invasiveness and placental angiogenesis, recruitment and instruction of immune cells so as to form a fetus-supporting milieu during pregnancy. The chemokine network is also involved in pregnancy complications.

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The CXCL12/CXCR4 axis is involved in the maintenance of Th2 bias at the maternal/fetal interface in early human pregnancy

Cited by 53 publications

References 35 publications

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

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

Decidual stromal cells recruit Th17 cells into decidua to promote proliferation and invasion of human trophoblast cells by secreting IL-17

The integrative roles of chemokines at the maternal–fetal interface in early pregnancy

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