NK cell abnormality and its treatment in women with reproductive failures such as recurrent pregnancy loss, implantation
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REVIEW ARTICLE
NK cell abnormality and its treatment in women with reproductive failures such as recurrent pregnancy loss, implantation failures, preeclampsia, and pelvic endometriosis Atsushi Fukui1 • Mai Kamoi1 • Ayano Funamizu1 • Kohei Fuchinoue1 • Hitomi Chiba1 • Megumi Yokota1 • Rie Fukuhara1 • Hideki Mizunuma1
Received: 26 December 2014 / Accepted: 31 March 2015 Ó Japan Society for Reproductive Medicine 2015
Abstract 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.
& Atsushi Fukui [email protected]; [email protected] 1
Department of Obstetrics and Gynecology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori 036-8562, Japan
Keywords Intralipid Intravenous immunoglobulin Natural cytotoxicity receptor NK cell Recurrent pregnancy loss
Introduction Natural killer (NK) cells play a very important role in human pregnancy. They bear a specific surface marker, CD56, and comprise 5–10 % of peripheral blood cells, 30–50 % of uterine endometrial cells, and 70 % of decidual lymphocytes. NK cells can be divided into CD56dim cells and CD56bright cells according to the intensity of their CD56 fluorescence. CD56bright cells account for 10 % of NK cells and are located mainly in the uterine endometrium and the decidua. Their main function is cytokine production. On the other hand, CD56dim cells account for 90 % of NK cells, representing the main population of circulating (peripheral blood) NK cells and showing high cytotoxicity. Moreover, NK cells express various kinds of activating and inhibitory receptors, and NK cell cytotoxicity is determined by the balance of these activating and inhibitory receptors. The regulation of uterine a
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