Galectin-9 Promotes Human Trophoblast Cell Invasion through Matrix Metalloproteinase-2 and p38 Signaling Pathway

Sun, Fang; Chen, Chun-Qing; Yu, Min; Wang, Songcun; Li, Da‐Jin; Du, Meirong

doi:10.4103/2096-2924.232880

Cited by 4 publications

(4 citation statements)

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“…Indeed, recent publications presented that miscarriages are associated with immune etiologies (150), where the development of the fetus and placenta is affected by either auto- or alloimmune rejection-type activity (151). Of interest, the expression of other galectins, although in modest extent, is also decreased at the maternal-fetal interface in spontaneous and recurrent miscarriages, including Gal-1, Gal-2, Gal-7, Gal-9, and Gal-10 (152–154). Furthermore, in good accordance, serum concentrations of Gal-1 and Gal-9 were also found to be decreased in miscarriage (99, 154, 155).…”

Section: Discussionmentioning

confidence: 99%

“…Of interest, the expression of other galectins, although in modest extent, is also decreased at the maternal-fetal interface in spontaneous and recurrent miscarriages, including Gal-1, Gal-2, Gal-7, Gal-9, and Gal-10 (152–154). Furthermore, in good accordance, serum concentrations of Gal-1 and Gal-9 were also found to be decreased in miscarriage (99, 154, 155). An elegant study revealed that Gal-1 has pivotal functions supporting maternal-fetal immune tolerance and its decreased expression leads to fetal loss in a mouse model.…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, Gal-9 was found to exert its functions in non-pregnant and pregnant states on NK cells, T cells, and B cells (101, 102, 147, 156–159). In addition, Gal-9 promotes trophoblast invasion in a Tim-3 dependent manner (154). Consistently, a higher proportion of decidual T cells that express activation markers (CD25, and CD69) was found in spontaneous abortion than in elective termination of pregnancy, and decidual lymphocytes from spontaneous abortion increased the apoptosis of trophoblast cells (160).…”

Section: Discussionmentioning

confidence: 99%

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Placental Galectins Are Key Players in Regulating the Maternal Adaptive Immune Response

et al. 2019

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Galectins are potent immunomodulators that regulate maternal immune responses in pregnancy and prevent the rejection of the semi-allogeneic fetus that also occurs in miscarriages. We previously identified a gene cluster on Chromosome 19 that expresses a subfamily of galectins, including galectin-13 (Gal-13) and galectin-14 (Gal-14), which emerged in anthropoid primates. These galectins are expressed only by the placenta and induce the apoptosis of activated T lymphocytes, possibly contributing to a shifted maternal immune balance in pregnancy. The placental expression of Gal-13 and Gal-14 is decreased in preeclampsia, a life-threatening obstetrical syndrome partly attributed to maternal anti-fetal rejection. This study is aimed at revealing the effects of Gal-13 and Gal-14 on T cell functions and comparing the expression of these galectins in placentas from healthy pregnancies and miscarriages. First-trimester placentas were collected from miscarriages and elective termination of pregnancies, tissue microarrays were constructed, and then the expression of Gal-13 and Gal-14 was analyzed by immunohistochemistry and immunoscoring. Recombinant Gal-13 and Gal-14 were expressed and purified, and their effects were investigated on primary peripheral blood T cells. The binding of Gal-13 and Gal-14 to T cells and the effects of these galectins on apoptosis, activation marker (CD25, CD71, CD95, HLA-DR) expression and cytokine (IL-1β, IL-6, IL-8, IL-10, IFNγ) production of T cells were examined by flow cytometry. Gal-13 and Gal-14 are primarily expressed by the syncytiotrophoblast at the maternal-fetal interface in the first trimester, and their placental expression is decreased in miscarriages compared to first-trimester controls. Recombinant Gal-13 and Gal-14 bind to T cells in a population- and activation-dependent manner. Gal-13 and Gal-14 induce apoptosis of Th and Tc cell populations, regardless of their activation status. Out of the investigated activation markers, Gal-14 decreases the cell surface expression of CD71, Gal-13 increases the expression of CD25, and both galectins increase the expression of CD95 on T cells. Non-activated T cells produce larger amounts of IL-8 in the presence of Gal-13 or Gal-14. In conclusion, these results show that Gal-13 and Gal-14 already provide an immunoprivileged environment at the maternal-fetal interface during early pregnancy, and their reduced expression is related to miscarriages.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Placental Galectins Are Key Players in Regulating the Maternal Adaptive Immune Response

et al. 2019

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“…Furthermore, early pregnancy loss or infertility cases might be connected to even weaker implantation and invasion. Research of the last decades emphasizes the importance of the interaction of trophoblast and decidua for controlling invasion depth and establishing a healthy placenta ( 7 – 9 ). Cases of the placenta accreta spectrum, in which the trophoblast might even invade neighboring organs, highlight the role of the decidua in this process as they commonly occur when the blastocyte implants at the site of a uterine scar, where decidua is absent ( 9 – 11 ).…”

Section: Introductionmentioning

confidence: 99%

Decidual γδT cells of early human pregnancy produce angiogenic and immunomodulatory proteins while also possessing cytotoxic potential

Nörenberg,

Vida,

Bösmeier

et al. 2024

Front. Immunol.

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During pregnancy, the maternal immune system must allow and support the growth of the developing placenta while maintaining the integrity of the mother’s body. The trophoblast’s unique HLA signature is a key factor in this physiological process. This study focuses on decidual γδT cell populations and examines their expression of receptors that bind to non-classical HLA molecules, HLA-E and HLA-G. We demonstrate that decidual γδT cell subsets, including Vδ1, Vδ2, and double-negative (DN) Vδ1-/Vδ2- cells express HLA-specific regulatory receptors, such as NKG2C, NKG2A, ILT2, and KIR2DL4, each with varying dominance. Furthermore, decidual γδT cells produce cytokines (G-CSF, FGF2) and cytotoxic mediators (Granulysin, IFN-γ), suggesting functions in placental growth and pathogen defense. However, these processes seem to be controlled by factors other than trophoblast-derived non-classical HLA molecules. These findings indicate that decidual γδT cells have the potential to actively contribute to the maintenance of healthy human pregnancy.

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Unraveling the molecular mechanisms driving enhanced invasion capability of extravillous trophoblast cells: a comprehensive review

Lin,

Wu,

Jiang

et al. 2024

J Assist Reprod Genet

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Galectin-9 Promotes Human Trophoblast Cell Invasion through Matrix Metalloproteinase-2 and p38 Signaling Pathway

Cited by 4 publications

References 1 publication

Placental Galectins Are Key Players in Regulating the Maternal Adaptive Immune Response

Placental Galectins Are Key Players in Regulating the Maternal Adaptive Immune Response

Decidual γδT cells of early human pregnancy produce angiogenic and immunomodulatory proteins while also possessing cytotoxic potential

Unraveling the molecular mechanisms driving enhanced invasion capability of extravillous trophoblast cells: a comprehensive review

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