NK22 Cells in the Uterine Mid-Secretory Endometrium and Peripheral Blood of Women with Recurrent Pregnancy Loss and Unexplained Infertility

J of Obstet and Gynaecol

Funamizu

Fukuhara

et al. 2017

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Aim: Natural cytotoxicity receptors (NCR) are unique markers that regulate natural killer (NK) cell cytotoxicity and cytokine production. In this study, we investigated the expression of NCR (NKp46, NKp44, and NKp30) and cytokine production in NK cells derived from the uterine endometrium of women with recurrent pregnancy loss (RPL). We also investigated the expression of NCR in peripheral blood NK cells in pregnant women with and without a history of RPL. Methods: The expression of NCR (NKp46, NKp44, and NKp30) in NK cells (CD56 dim and CD56 bright ) in the uterine endometrium was analyzed using 3-color flow cytometry. Cytokine (tumor necrosis factor-α and interferon-γ) production was also analyzed. NK cells from the mid-secretory endometrium of 28 women with RPL, 34 women with implantation failure, and 74 controls were collected and mechanically dispersed using a tissue grinder. The expression of NCR in peripheral blood NK cells from pregnant women with (n = 17) and without (n = 91) a history of RPL was analyzed. Results: The percentages of NKp46 + NK cells were significantly lower in both women with RPL and pregnant women with a history of RPL. The percentages of tumor necrosis factor-α-and/or interferon-γ-producing uterine endometrial NK cells were significantly lower in women with RPL compared with controls. Conclusion: The changes in NCR expression and cytokine production, especially decreased NKp46 expression in endometrial NK cells, suggests the presence of abnormal NK cell regulation in women with reproductive failures.

Section: Discussionmentioning

confidence: 91%

Expression of natural cytotoxicity receptors and cytokine production on endometrial natural killer cells in women with recurrent pregnancy loss or implantation failure, and the expression of natural cytotoxicity receptors on peripheral blood natural killer cells in pregnant women with a history of recurrent pregnancy loss

J of Obstet and Gynaecol

Funamizu

Fukuhara

et al. 2017

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“…suggested that NK22 cells produce IL‐22 and other cytokines that prevent inflammation and protect mucosal sites in tonsils or Peyer's patches . We previously reported the higher production of UE NK22 cells in women with RPL . NK22 cells are presumed to increase to normalize or regulate cytokine production in women with RPL.…”

Section: Introductionmentioning

confidence: 99%

“…It has been reported that NK22 cells in the human UE express NKp46 . Previously, we reported that NK22 cells express NKp46 …”

Section: Introductionmentioning

confidence: 99%

Expression of retinoid‐related orphan receptor (ROR)γt on NK22 cells in the peripheral blood and uterine endometrium of women with unexplained recurrent pregnancy loss and unexplained infertility

Fuchinoue

J of Obstet and Gynaecol

Chiba

et al. 2016

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“…These findings shed some light on the relationships existing between NKp46 ? NK cells, production of cytokines (IFNc and TNFa) by NK cells, and NK22 cells [41]. We speculated that in normal pregnancy, NK22 cells could produce IL-22 whereas conventional NK cells produce IFNc and TNFa.…”

Section: Nk22 Cells and Reproductionmentioning

confidence: 99%

“…We have evaluated the physiological role of NK22 cells in women with and without unexplained RPL using samples of pre-pregnancy peripheral blood and midsecretory uterine endometrium [41]. The relative proportions of NK22 cells in both peripheral blood and uterine endometrium were significantly higher in women with RPL than in women without RPL.…”

Section: Nk22 Cells and Reproductionmentioning

confidence: 99%

NK cell abnormality and its treatment in women with reproductive failures such as recurrent pregnancy loss, implantation failures, preeclampsia, and pelvic endometriosis

Reprod Medicine & Biology

Kamoi

Funamizu

et al. 2015

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The regulation of uterine and peripheral blood natural killer (NK) cells has been associated with problems related to reproductive immunology such as recurrent pregnancy loss (RPL), implantation failure or preeclampsia. NKp46, one of the natural cytotoxicity receptors (NCRs), is a unique marker that functions in NK cell cytotoxicity and cytokine production. Expression of NKp46 on NK cells is lower in women with recurrent pregnancy loss and pregnancy-induced hypertension. Moreover, expression of NKp46 on peritoneal fluid NK cells is lower in women with pelvic endometriosis. Therefore, evaluation of NKp46 on peripheral blood NK cells may provide a means of screening for reproductive abnormalities. Recently, a new type of NK cell, the NK22 cell, has been reported. This cell may be a regulator not only of the mucosal barrier but also of reproduction. For women with RPL showing abnormal uterine and/or peripheral blood NK cells, both intravenous immunoglobulin treatment and intralipid treatment have been reported. The effects of these treatments are still controversial, and further studies are needed in order to clarify their true impact. The present review examines variations in the expression of NCRs on NK cells, the participation of NK22 cells in reproduction, and the possible use of intravenous immunoglobulin or intralipid treatment for women with recurrent pregnancy loss and NK cell abnormality.