Update on pathways regulating the activation of uterine Natural Killer cells, their interactions with decidual spiral arteries and homing of their precursors to the uterus

Croy, B. Anne; Esadeg, Souad; Chantakru, Sirirak; Heuvel, Mieke van den; Paffaro, Valdemar A.; He, Hong; Black, Gordon P.; Ashkar, Ali A.; Kiso, Yasuo; Zhang, Jianhong

doi:10.1016/s0165-0378(03)00046-9

Cited by 172 publications

(114 citation statements)

References 51 publications

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“…Unlike peripheral natural killer cells, the uNK cells are not cytotoxic and their main biological functions are to produce immunotrophic and angiogenic cytokines. The activation of adequate uNK cells is important for maternal tolerance during the implantation window 31, 32, 33. However, once the uNK cells are highly activated, a Th1 pro‐inflammatory condition is induced, with the local production of IFN‐ γ and TNF‐ α 34, 35.…”

Section: Discussionmentioning

confidence: 99%

Thin endometrium transcriptome analysis reveals a potential mechanism of implantation failure

Maekawa

Tanaka

Mihara

et al. 2017

Reprod Medicine & Biology

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AimAlthough a thin endometrium has been well recognized as a critical factor in implantation failure, little information is available regarding the molecular mechanisms. The present study investigated these mechanisms by using genome‐wide mRNA expression analysis.MethodsThin and normal endometrial tissue was obtained from a total of six women during the mid‐luteal phase of the menstrual cycle. The transcriptomes were analyzed with a microarray. Differentially expressed genes were classified according to Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways.ResultsThe study identified 318 up‐regulated genes and 322 down‐regulated genes in the thin endometrium, compared to the control endometrium. The GO and KEGG pathway analyses indicated that the thin endometrium possessed aberrantly activated immunity and natural killer cell cytotoxicity that was accompanied by an increased number of inflammatory cytokines, such as IFN‐γ. Various genes that were related to metabolism and anti‐oxidative stress were down‐regulated in the thin endometrium.ConclusionImplantation failure in the thin endometrium appears to be associated with an aberrantly activated inflammatory environment and aberrantly decreased response to oxidative stress.

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Section: Discussionmentioning

confidence: 99%

Thin endometrium transcriptome analysis reveals a potential mechanism of implantation failure

Maekawa

Tanaka

Mihara

et al. 2017

Reprod Medicine & Biology

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“…Approximately 70% of the leukocytes in early decidua are uterine NK cells that are likely involved in fine tuning placental development, vascularity and subsequently fetal growth. [61][62][63] Unlike most cells of the human body, trophoblasts have limited or poor expression of the major histocompatibility antigens-human leukocyte antigen (HLA)-A and -B that are highly polymorphic. Limited or poor expression of HLA-A and -B is postulated to support the development of maternal tolerance to the fetus during pregnancy.…”

Section: Micrornas and Immune Cells At The Maternal-fetal Interfacementioning

confidence: 99%

MicroRNAs, immune cells and pregnancy

et al. 2014

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MicroRNAs (miRNAs) are a recently discovered class of non-coding RNAs that are expressed in many cell types, where they regulate the expression of complementary RNAs, thus modulating the stability and translation of mRNAs. miRNAs are predicted to regulate the expression of ,50% of all protein coding genes in mammals. Therefore, they participate in virtually all cellular processes investigated so far. Altered miRNAs expressions are associated with both physiological (pregnancy) and pathological processes (cancer). As the dynamic maternal-fetal interface plays a critical role in the maintenance of successful pregnancy, it is not surprising that the miRNAs that are unique to reproductive tissues are abundantly expressed. Research in this field has demonstrated the presence and dysregulation of a distinct set of pregnancy-associated miRNAs; however, most studies have centered on localizing various miRNAs in reproductive microdomains associated with normal or complicated pregnancies. Although several independent miRNA regulatory mechanisms associated with endometrial receptivity, immune cells, angiogenesis and placental development have been studied, miRNA-mediated regulation of pregnancy remains poorly understood. This review provides a summary of the current data on miRNA regulation as well as functional profiles of miRNAs that are found in the uterus, in immune cells associated with maternal tolerance to the fetus, and those involved in angiogenesis and placental development.

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“…6 In this regard, studies in mice identified spiral artery remodeling as a major uterine NK function that results in the conversion of maternal vessels to lowresistance, high-volume conduits to increase blood supply to the fetus. 7 NK CELLS IN PREGNANCY NK cells are the dominant lymphocyte population that accumulates in the decidua basalis of a healthy pregnancy. At this site, NK cells are CD56 bright and CD16 neg and phenotypically distinct from peripheral blood NK cells that are predominantly CD56 dim and CD16 1 .…”

Section: Introductionmentioning

confidence: 99%

HLA-G-mediated NK cell senescence promotes vascular remodeling: implications for reproduction

Rajagopalan

2014

Cell Mol Immunol

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The uterus in early pregnancy is a non-lymphoid organ that is enriched in natural killer (NK) cells. Studies to address the role of these abundant human NK cells at the maternal/fetal interface have focused on their response to the major histocompatibility complex (MHC) molecules on fetal trophoblast cells that they contact. The interaction of maternal NK cell receptors belonging to the killer cell immunoglobulin-like receptor (KIR) family with trophoblast MHC class I molecules in pregnancy can regulate NK cell activation for secretion of pro-angiogenic factors that promote placental development. This review will cover the role of KIR at the maternal/fetal interface and focus on KIR2DL4, a KIR family member that is uniquely poised to play a role in pregnancy due to the restricted expression of its ligand, human leukocyte antigen (HLA)-G, by fetal trophoblast cells early in pregnancy. The pathways by which KIR2DL4-HLA-G interactions induce the cellular senescence of NK cells and the role of the resulting senescence-associated secretory phenotype (SASP) in vascular remodeling will be discussed in the context of reproduction.

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Update on pathways regulating the activation of uterine Natural Killer cells, their interactions with decidual spiral arteries and homing of their precursors to the uterus

Cited by 172 publications

References 51 publications

Thin endometrium transcriptome analysis reveals a potential mechanism of implantation failure

Thin endometrium transcriptome analysis reveals a potential mechanism of implantation failure

MicroRNAs, immune cells and pregnancy

HLA-G-mediated NK cell senescence promotes vascular remodeling: implications for reproduction

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