Evaluation of <scp>NKp46</scp> expression and cytokine production of decidual <scp>NK</scp> cells in women with recurrent pregnancy loss

Yamamoto, Mayu; Fukui, Atsushi; Mai, Chuxian; Saeki, Shinichiro; Takayama, Ryu; Wakimoto, Yu; Yamaya, Ayano; Kwak‐Kim, Joanne; Shibahara, Hiroaki

doi:10.1002/rmb2.12478

Cited by 6 publications

(4 citation statements)

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“…At least three different subsets of NK cells (p46neg, p46dim and p46++) can be distinguished based on NKp46 expression [23][24][25]. Recent works have suggested that these subsets differ not only in terms of phenotypes but also in terms of functions [16,26]. It has been shown that decidual NKp46 bright cells are related to cytokine production, and in women with recurrent pregnancy loss with karyotypically normal pregnancies, a reduction in NKp46 bright cells is thought to cause abnormal cytokine production (NK1 shift), thus leading to a miscarriage [16,26].…”

Section: Discussionmentioning

confidence: 99%

“…NKp46, also known as natural cytotoxicity receptor 1 (NCR1), is expressed by NK cells and has a crucial role in the antitumor activity, antiviral activity and autoimmune setting of NK cells [12,13]. A growing number of studies suggest that accentuations of NKp46 expression are associated with reproductive failures, such as recurrent pregnancy failures and implantation failures [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

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A Blinded Investigation: Accentuated NK Lymphocyte CD335 (NKp46) Expression Predicts Pregnancy Failures

et al. 2023

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Aim: NKp46 is an NK cell receptor uniquely expressed by NK cells and a small subset of innate lymphoid cells. In our previous studies, we suggested a tight connection between the activity of NK cells and the expression of NKp46 and supported the clinical significance of NKp46 expression in NK cells in women with reproductive failures. In this study, we investigated the expression of NKp46 in NK cells in the peripheral blood of women in early pregnancy and analyzed its association with pregnancy loss. Methods: In a blinded study, we examined blood samples and analyzed the subsequent pregnancy outcomes from 98 early pregnant women (5th–7th week of gestation—w.g.) and 66 women in the 11th–13th week of pregnancy who served as controls. We studied the expression of NKp46 and the levels of anti-cardiolipin antibodies (aCL). The results of aCL were shared with the clinic, while the expression of NKp46 was blinded and not analyzed until the end of the study. Results: A misbalance in the NKp46+NK cells subpopulations was associated with an unfavorable ongoing pregnancy. A decreased level of NKp46high cells (<14%) was strongly associated with miscarriage. A decreased level of the double-bright subpopulation (NKp46hightCD56++) also was a negative prognostic factor for the pregnancy course, but its increased level (>4%) was strongly associated with a successful pregnancy course. Conclusions: Our results showed that accentuated levels of NKp46+NK cells lead to a negative prognosis for early pregnancy courses in women.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Blinded Investigation: Accentuated NK Lymphocyte CD335 (NKp46) Expression Predicts Pregnancy Failures

et al. 2023

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“…NKp30a and NKp30b transmit activation signals, while NKp30c transmit suppression signals; NCR1 and NCR2 were also transcribed into several isomers, but no functional differences of splicing variants were found in NCR1, and there were inhibitory isomers in NCR2 [22] . In addition, all three kinds of NCRS have been repeatedly shown to induce cytotoxic effect of uterine NK cells and cytokine production, but only NKp46 can induce cytotoxic effect of DNK cells [23] . In addition, NKp30 can promote the secretion of cytokines, while NKp44 has inhibitory function in DNK cells [22] .…”

Section: Natural Cytotoxicity Receptors(ncr)mentioning

confidence: 99%

Research progress in the mechanism of action of NK cell-related receptors during recurrent spontaneous abortion

2023

AJMHS

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Recurrent spontaneous abortion (RSA) refers to multiple spontaneous abortions with the same sexual partner; In 2020, Chinese expert consensus suggested that it should be defined as the loss of the embryo or fetus before 28 weeks of gestation with the same sexual partner for two or more times in a row, including the biochemical pregnancy that occurred several times in a row. The pathogenesis of RSA is complex and diverse. At present, the pathogenesis factors have been widely recognized by the industry, including genetic factors, endocrine factors, anatomical abnormalities, infectious factors and immune factors. Among them, the role of immune factors such as T lymphocytes, dendritic cells and natural killer cells (NK) in the occurrence and development of RSA has attracted wide attention, especially NK cells. NK cells are an important part of human immune system. The specific surface molecules of Decidual natural killer cell (dNK) play an immunomodulatory role in the invasion of trophoblast cells and the remodeling of uterine spiral artery during pregnancy, which is particularly important in the early gestation period. The function of dNK cells is tightly regulated by a balance between activation and inhibition signals transmitted by the various family of receptors (NK cell receptors, NKRS) that DNK cells express. In this paper, the existing research progress of decidual NK cells on the mechanism of its receptors in the process of recurrent spontaneous abortion will be reviewed as follows.

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“…In URSA patients, the NK1/NK2 ratio of dNK cells (producing IFN-γ/IL-4 NK cell ratio) increased, and it was independent of whether the karyotype was normal. NKp46 is a receptor on NK cells, which is involved in cytotoxicity and cytokine production [24]. A study showed that in women with low %NKp46 + dNK, the ratio of NK1/NK2 was significantly higher than that of women with high %NKp46 + dNK, and the threshold of %NKp46 + dNK cells was 86.52% [25].…”

Section: Nk Cellsmentioning

confidence: 99%

Research progress of immune balance and genetic polymorphism in unexplained recurrent abortion

Kang,

Xie,

Chen

et al. 2023

Explor Immunol

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The etiology of recurrent spontaneous abortion (RSA) is extremely complex, as there are 40–50% of patients with unexplained miscarriages, known as unexplained RSA (URSA). URSA affects approximately 1–2% of females of childbearing age and has a massive impact on the physical and mental conditions of both patients and their families. The pathogenesis of the disease remains unclear, making its treatment complicated. In recent years, considerable progress has been made in the exploration of the URSA immune balance mechanism and it has been universally acknowledged that a balanced immune response (as abnormal immunity) may be the root cause of poor pregnancy outcomes. This review discussed and summarized the effects of immune cells and blocking antibodies (BAs) on URSA based on the current state of knowledge in this area. Additionally, molecular genetics also plays an essential role in the incidence rate of URSA since the role of genetic polymorphism in the pathogenesis of URSA has been thoroughly studied. Nonetheless, the outcomes of these studies are inconsistent, particularly across populations. This paper reviewed previous studies on URSA and maternal genetic polymorphism, focusing on and synthesizing the most important findings to date, and providing diagnostic recommendation for URSA patients with clinical symptoms.

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Evaluation of NKp46 expression and cytokine production of decidual NK cells in women with recurrent pregnancy loss

Cited by 6 publications

References 40 publications

A Blinded Investigation: Accentuated NK Lymphocyte CD335 (NKp46) Expression Predicts Pregnancy Failures

A Blinded Investigation: Accentuated NK Lymphocyte CD335 (NKp46) Expression Predicts Pregnancy Failures

Research progress in the mechanism of action of NK cell-related receptors during recurrent spontaneous abortion

Research progress of immune balance and genetic polymorphism in unexplained recurrent abortion

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