The Role of Tim-3 on dNK Cells Dysfunction During Abnormal Pregnancy With Toxoplasma gondii Infection

Li, Teng; Cui, Lijun; Xu, Xiaoyan; Zhang, Haixia; Jiang, Yuzhu; Ren, Lele; Yang, Chunyan; Liu, Xianbing; Hu, Xuemei

doi:10.3389/fcimb.2021.587150

Cited by 13 publications

(25 citation statements)

References 52 publications

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“…It is a controversial receptor with uncertain inhibition or activation functionality, and binds to HLA-G monomers or dimers. These 'HLA-G/KIR2DL4' combinations are able to result in the production of pro-inflammatory cytokines like IFN-g for driving cells into an immunosuppressive phase (134). KIR2DL4 could be also observed in mast cells recently (135).…”

Section: Hla-g Acting In the Pregnancy Microenvironmentmentioning

confidence: 99%

HLA-G: An Important Mediator of Maternal-Fetal Immune-Tolerance

2021

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Maternal-fetal immune-tolerance occurs throughout the whole gestational trimester, thus a mother can accept a genetically distinct fetus without immunological aggressive behavior. HLA-G, one of the non-classical HLA class I molecules, is restricted-expression at extravillous trophoblast. It can concordantly interact with various kinds of receptors mounted on maternally immune cells residing in the uterus (e.g. CD4+ T cells, CD8+ T cells, natural killer cells, macrophages, and dendritic cells) for maintaining immune homeostasis of the maternal-fetus interface. HLA-G is widely regarded as the pivotal protective factor for successful pregnancies. In the past 20 years, researches associated with HLA-G have been continually published. Indeed, HLA-G plays a mysterious role in the mechanism of maternal-fetal immune-tolerance. It can also be ectopically expressed on tumor cells, infected sites and other pathologic microenvironments to confer a significant local tolerance. Understanding the characteristics of HLA-G in immunologic tolerance is not only beneficial for pathological pregnancy, but also helpful to the therapy of other immune-related diseases, such as organ transplant rejection, tumor migration, and autoimmune disease. In this review, we describe the biological properties of HLA-G, then summarize our understanding of the mechanisms of fetomaternal immunologic tolerance and the difference from transplant tolerance. Furthermore, we will discuss how HLA-G contributes to the tolerogenic microenvironment during pregnancy. Finally, we hope to find some new aspects of HLA-G in fundamental research or clinical application for the future.

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Section: Hla-g Acting In the Pregnancy Microenvironmentmentioning

confidence: 99%

HLA-G: An Important Mediator of Maternal-Fetal Immune-Tolerance

2021

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“…IL-10 is an immunoregulatory cytokine whose production has been demonstrated in dNK cells [38] and decidual macrophages [18]. IL-10 was found to affect the interaction of dNK cells and the dendritic cells of the uteroplacental complex in a mouse model [39].…”

Section: Discussionmentioning

confidence: 99%

Pro- and Anti-Inflammatory Cytokines in the Context of NK Cell–Trophoblast Interactions

Михайлова

Grebenkina

Khokhlova

et al. 2022

IJMS

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During pregnancy, uterine NK cells interact with trophoblast cells. In addition to contact interactions, uterine NK cells are influenced by cytokines, which are secreted by the cells of the decidua microenvironment. Cytokines can affect the phenotypic characteristics of NK cells and change their functional activity. An imbalance of pro- and anti-inflammatory signals can lead to the development of reproductive pathology. The aim of this study was to assess the effects of cytokines on NK cells in the presence of trophoblast cells in an in vitro model. We used TNFα, IFNγ, TGFβ and IL-10; the NK-92 cell line; and peripheral blood NK cells (pNKs) from healthy, non-pregnant women. For trophoblast cells, the JEG-3 cell line was used. In the monoculture of NK-92 cells, TNFα caused a decrease in CD56 expression. In the coculture of NK cells with JEG-3 cells, TNFα increased the expression of NKG2C and NKG2A by NK-92 cells. Under the influence of TGFβ, the expression of CD56 increased and the expression of NKp30 decreased in the monoculture. After the preliminary cultivation of NK-92 cells in the presence of TGFβ, their cytotoxicity increased. In the case of adding TGFβ to the PBMC culture, as well as coculturing PBMCs and JEG-3 cells, the expression of CD56 and NKp44 by pNK cells was reduced. The differences in the effects of TGFβ in the model using NK-92 cells and pNK cells may be associated with the possible influence of monocytes or other lymphoid cells from the mononuclear fraction.

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“…Dysregulation of Tim-3 expression on decidual NK (dNK) cells and decidual macrophages was observed in several cases of pregnancy complications. Tim-3 −/− pregnant mice displayed more worse pregnancy outcomes with T. gondii infection ( Zhang D et al, 2019 ; Li et al, 2021 ). LILRB 4 expressed by macrophages and dendritic cells plays an important immune-regulatory role at the maternal–fetal interface.…”

Section: Discussionmentioning

confidence: 99%

Toll-Like Receptor 2 is Involved in Abnormal Pregnancy in Mice Infected with Toxoplasma gondii During Late Pregnancy

et al. 2021

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Infection with Toxoplasma gondii during pregnancy causes failure of pregnancy maintenance, resulting in fetal death, abortion, stillbirth, or premature birth, but the mechanism of disease onset remains unclear. Although Toll-like receptor 2 (TLR2) is expressed on antigen-presenting cells and trophoblasts, the role of TLR2 in T. gondii infection during pregnancy is unknown. In this study, we investigated the role of TLR2 in congenital toxoplasmosis using TLR2-deficient (TLR2−/−) mice. T. gondii infection on gestational day 12.5 (Gd12.5) induced more abnormal pregnancy, including premature birth and stillbirth, in wild-type mice than in TLR2−/− mice. Multiple calcifications were observed in the placentas of the infected wild-type mice. At Gd18.5 (6days postinfection), the parasite numbers in the placenta and uterus and the histological changes did not differ significantly between the wild-type and TLR2−/− mice. However, T. gondii infection reduced the mRNA expression of interleukin-12p40 (IL-12p40) and increased IL-4 and IL-10 mRNAs in the placentas of the wild-type mice. In contrast, the placentas of the TLR2−/− mice showed no changes in the expression of these cytokines, including IL-6 and tumor necrosis factor α, in response to T. gondii infection. Serum interferon-γ levels were significantly lower in the infected TLR2−/− mice than in the infected wild-type mice on Gd18.5. Thus, the TLR2−/− mice were less susceptible to the induction of immune responses by T. gondii infection during late pregnancy. Therefore, TLR2 signaling may play a role in the development of disease states during pregnancy, specifically placental hypofunction.

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The Role of Tim-3 on dNK Cells Dysfunction During Abnormal Pregnancy With Toxoplasma gondii Infection

Cited by 13 publications

References 52 publications

HLA-G: An Important Mediator of Maternal-Fetal Immune-Tolerance

HLA-G: An Important Mediator of Maternal-Fetal Immune-Tolerance

Pro- and Anti-Inflammatory Cytokines in the Context of NK Cell–Trophoblast Interactions

Toll-Like Receptor 2 is Involved in Abnormal Pregnancy in Mice Infected with Toxoplasma gondii During Late Pregnancy

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