The Role of Uterine NK Cells in Normal Reproduction and Reproductive Disorders

Bulmer, Judith N.; Lash, Gendie E.

doi:10.1007/978-3-319-18881-2_5

Cited by 31 publications

(25 citation statements)

References 188 publications

(208 reference statements)

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“…The dominant immune cells in the first trimester are a type of innate lymphoid cell known as uterine natural killer (uNK) cells (Bulmer and Lash, 2015;Moffett and Colucci, 2015;Vacca et al, 2019). These cells make up ∼70% of immune cells in the uterine environment, while macrophages account for ∼20% and T cells for ∼10%.…”

Section: Uterine Leukocytes and Other Immune Cellsmentioning

confidence: 99%

Development of the human placenta

2019

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The placenta is essential for normal in utero development in mammals. In humans, defective placental formation underpins common pregnancy disorders such as pre-eclampsia and fetal growth restriction. The great variation in placental types across mammals means that animal models have been of limited use in understanding human placental development. However, new tools for studying human placental development, including 3D organoids, stem cell culture systems and single cell RNA sequencing, have brought new insights into this field. Here, we review the morphological, molecular and functional aspects of human placental formation, with a focus on the defining cell of the placentathe trophoblast.

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Section: Uterine Leukocytes and Other Immune Cellsmentioning

confidence: 99%

Development of the human placenta

2019

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“…As modified percentages of NK cells in the endometrium of women with reproductive failure including infertility, recurrent implantation failure, recurrent miscarriage, and preeclampsia have been suggested to play a role in their pathogenesis 24 and as uterine NK cell functions have been shown to be affected by HHV-6…”

Section: Re Sultsmentioning

confidence: 99%

Prevalence of HHV‐6 in endometrium from women with recurrent implantation failure

Coulam

Bilal

Garcia

et al. 2018

American J Rep Immunol

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“…1 Uterine NK (uNK) cells are an immune cell type exclusively found in the FRT and they differ from their blood NK cell counterparts in that the former are predominantly CD16-CD56 bright , whereas the latter are predominantly CD16+CD56 dim and more cytotoxic. 4 In humans, uNK cells numbers fluctuate throughout the menstrual cycle, representing over 30% of all endometrial cells by late secretory phase.…”

mentioning

confidence: 99%

Type I IFNs in the female reproductive tract: The first line of defense in an ever-changing battleground

Cumming

Bourke

2018

Journal of Leukocyte Biology

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The primary function of the female reproductive tract (FRT) is to enable successful reproduction, yet the biologic mechanisms required to accomplish this, which include fluctuating sex hormones and tolerance of semen and a semi-allogeneic fetus, can leave this unique mucosal environment susceptible to pathogenic challenge. Consequently, the FRT has evolved specialized innate and adaptive immune responses tailored to protecting itself from infection without compromising reproductive success. A family of innate immune cytokines that has emerged as important regulators of these immune responses is the type I IFNs. Type I IFNs are typically rapidly produced in response to pathogenic stimulation and are capable of sculpting pleotropic biologic effects, including immunomodulation, antiproliferative effects, and inducing antiviral and bactericidal molecules. Here, we review what is currently known about type I IFN-mediated immunity in the FRT in human, primate, and murine models and explore their importance with respect to three highly relevant FRT infections: HIV, Zika, and Chlamydia. K E Y W O R D SChlamydia, female reproductive tract, HIV, hormonal regulation, mucosal immunity, Type I IFNs, Zika THE FRT: A DYNAMIC IMMUNE ENVIRONMENTThe female reproductive tract (FRT) is a site of unique mucosal immune regulation; it must be capable of detecting and inducing immune responses against pathogenic infections yet maintain tolerance to commensal bacteria, semen, and the semi-allogeneic fetus. The FRT can be broadly divided into two main anatomic sites: the lower reproductive tract, which includes the vagina and ectocervix, and the upper reproductive tract, which includes the uterus, fallopian tubes, and ovaries. The structure of the lining of the FRT varies considerably between these sites and reflects their respective functional characteristics. The lining of the lower FRT comprises multilayered squamous epithelium, which represents a large barrier defense and supports high levels of commensal microbes. In contrast, the upper FRT comprises a single layer of columnar epithelium, which is remodeled in response to sex hormones to enable support of successful implantation and pregnancy. 1 Between these two sites of the FRT is the transformation zone, where the squamous epithelium of the ectocervix meets the columnar epithelium of the endocervix. FRT immunity is predominately mediated by both epithelial cells and the immune cells that underlie the epithelium in both the upper and lower reproductive tract. REGULATION OF FRT IMMUNITY: SEX HORMONESAn important aspect of immunoregulation within the FRT is that the FRT immune cells are continuously modulated in response to fluctuating levels of the sex hormones estrogen (E2) and progesterone (P4) during the menstrual cycle. The first line of defense against pathogen infection is usually the epithelial cells that line the upper and lower FRT. Epithelial cells that line the vagina and uterus are important regulators of immunity in the mucosa, acting through specialized antigen present...

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The Role of Uterine NK Cells in Normal Reproduction and Reproductive Disorders

Cited by 31 publications

References 188 publications

Development of the human placenta

Development of the human placenta

Prevalence of HHV‐6 in endometrium from women with recurrent implantation failure

Type I IFNs in the female reproductive tract: The first line of defense in an ever-changing battleground

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