NK cells that differ in expression of NKp46 might play different roles in endometrium

Mai, Chuxian; Fukui, Atsushi; Takeyama, Ryu; Yamamoto, Mayu; Saeki, Shinichiro; Yamaya, Ayano; Kato, Toru; Ukita, Yuji; Wakimoto, Yu; Shibahara, Hiroaki

doi:10.1016/j.jri.2021.103367

Cited by 10 publications

(7 citation statements)

References 41 publications

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“…Uterine natural killer (uNK) cells play a critical role in maintaining pregnancy by secreting various regulatory factors that manipulate placental invasion and maternal vascular development. [ 43 ] Low expression of NKp46 or CD49b, surrogate markers for activating receptor [ 44 ] or mature NK cells, [ 45 ] respectively, in uNK cells reportedly produces poor reproductive outcomes; uNK cells generally show low cytotoxic activity compared to peripheral NK (pNK) cells, displaying a low expression of CD107a as a marker of degranulation. [ 46 ] We next examined the molecular features of NK cells those are resident or trapped in the uterus, based on the presence or absence of UdECM administration.…”

Section: Resultsmentioning

confidence: 99%

Uterus‐Derived Decellularized Extracellular Matrix‐Mediated Endometrial Regeneration and Fertility Enhancement

Ahn

Sen

Lee

et al. 2023

Adv Funct Materials

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Tissue‐specific decellularized extracellular matrix recapitulates the complexity of natural ECMs, creating an organ‐specific microenvironment based on its intrinsic characteristics. Here, hydrogels containing uterus‐derived decellularized extracellular matrix (UdECMs) from the endometrium‐specific layer or the entire uterus are developed. UdECMs serve as effective organ‐specific biomaterials, displaying that intrauterine UdECM administration induces endometrial regeneration and fertility enhancement. Moreover, UdECM administration alters the profile of natural killer cell subpopulations to exhibit more mature and less cytotoxic features, providing a favorable uterine environment for successful implantation and decidualization. Interestingly, insulin‐like growth factor 1 and insulin‐like growth factor‐binding protein 3 as key regulatory factors that contribute to UdECM‐mediated endometrial regeneration are discovered. Furthermore, ex vivo culture of human uterine tissues reveals that UdECMs of different origins exhibit distinct therapeutic effects based on the endometrial conditions of patients, suggesting their uses as a therapeutic intervention providing personalized regenerative medicine for infertile patients with a poor uterine environment.

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Section: Resultsmentioning

confidence: 99%

Uterus‐Derived Decellularized Extracellular Matrix‐Mediated Endometrial Regeneration and Fertility Enhancement

Ahn

Sen

Lee

et al. 2023

Adv Funct Materials

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“…In addition, it is expressed on ILCs and γδ T cells 30 . NKp46 dim and NKp46 bright uNK cells have different roles; NKp46 dim uNK cells primarily have a cytotoxic function, while NKp46 bright uNK cells are involved in cytokine production 21 . However, its relationship to reproduction remains unclear.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, we reported that the numbers of NKp46 + CD16 − NK cells were low in patients with higher CD56 dim /CD16 + NK cells, accompanied by an NK2 shift 20 . We have also reported that NKp46 dim NK cells may be involved in NK cell cytotoxicities, whereas NKp46 bright NK cells may be involved in cytokine production, suggesting that NKp46 could be a predictive marker for immune tolerance in pregnancy 21 …”

Section: Introductionmentioning

confidence: 91%

“…20 We have also reported that NKp46 dim NK cells may be involved in NK cell cytotoxicities, whereas NKp46 bright NK cells may be involved in cytokine production, suggesting that NKp46 could be a predictive marker for immune tolerance in pregnancy. 21 There are two types of NK cells: NK1 cells producing inflammatory (Type 1) cytokines, such as IFNγ and TNFα, and NK2 cells producing anti-inflammatory (Type 2) cytokines, such as IL-4 and IL-10. 22 NK cells show polarities in their cytokine secretion profiles, comparable to the polarities of T helper (Th) cells.…”

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confidence: 99%

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

Yamamoto¹,

Fukui²,

Mai³

et al. 2022

Reprod Medicine & Biology

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Recurrent pregnancy loss (RPL) is defined as two or more clinical pregnancy losses. 1 Approximately 60% of patients with RPL have repeated, unexplained miscarriages without common diagnoses, such as uterine malformation, the presence of antiphospholipid antibodies, thyroid dysfunction, or abnormal karyotypes in couples. 2 Such unexplained miscarriages are possibly due to fetal chromosomal abnormalities or dysfunctional maternal immune responses.An embryo is a semi-allograft with paternal alloantigens recognized by the maternal immune system. 3,4 In early pregnancy, the inflammatory immune response is necessary for successful implantation. In particular, cytotoxic immune effectors at the maternal-fetal interface protect a fetus from pathogens while participating in tissue

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“…In one study, NKp46 + eNK cells were classified into low-expression (NKp46 dim eNK) and high-expression (NKp46 bright eNK) groups according to different fluorescence intensities. NKp46 dim eNK cells were reportedly involved in cell killing and NKp46 bright eNK cells in cytokine production, demonstrating that these two clusters play different roles in the immune regulation of the endometrium ( 129 ). Further studies are needed to verify the relevance of NKp46 in RM, and consistent criteria need to be applied.…”

Section: Unk Cells Under Pathological Conditionsmentioning

confidence: 99%

Uterine Natural Killer Cells: A Rising Star in Human Pregnancy Regulation

Xie

Meng

et al. 2022

Front. Immunol.

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Uterine natural killer (uNK) cells are an immune subset located in the uterus. uNK cells have distinct tissue-specific characteristics compared to their counterparts in peripheral blood and lymphoid organs. Based on their location and the pregnancy status of the host, uNK cells are classified as endometrial NK (eNK) cells or decidua NK (dNK) cells. uNK cells are important in protecting the host from pathogen invasion and contribute to a series of physiological processes that affect successful pregnancy, including uterine spiral artery remodeling, fetal development, and immunity tolerance. Abnormal alterations in uNK cell numbers and/or impaired function may cause pregnancy complications, such as recurrent miscarriage, preeclampsia, or even infertility. In this review, we introduce recent advances in human uNK cell research under normal physiological or pathological conditions, and summarize their unique influences on the process of pregnancy complications or uterine diseases. Finally, we propose the potential clinical use of uNK cells as a novel cellular immunotherapeutic approach for reproductive disorders.

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NK cells that differ in expression of NKp46 might play different roles in endometrium

Cited by 10 publications

References 41 publications

Uterus‐Derived Decellularized Extracellular Matrix‐Mediated Endometrial Regeneration and Fertility Enhancement

Uterus‐Derived Decellularized Extracellular Matrix‐Mediated Endometrial Regeneration and Fertility Enhancement

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

Uterine Natural Killer Cells: A Rising Star in Human Pregnancy Regulation

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