Author/Editor		Feyaerts, D.; Kuret, Tadeja; Cranenbroek, B. van; Zeeuw-Hingrez, S. van der; Van der Heijden, O.W.H.; Van der Meer, A.; Joosten, I.; Van der Molen, R.G.
Title		Endometrial natural killer (NK) cells reveal a tissue-specific receptor repertoire
Type		članek
Vol. and No.		Letnik 33, št. 3
Publication year		2018
Volume		str. 441-451
ISSN		0268-1161 - Human reproduction (Oxford, England)
Language		eng
Abstract		Study question : Is the natural killer (NK) cell receptor repertoire of endometrial NK (eNK) cells tissue-specific? Summary answer : The NK cell receptor (NKR) expression profile in pre-pregnancy endometrium appears to have a unique tissue- speci fi c phenotype, different from that found in NK cells in peripheral blood, suggesting that these cells are fi nely tuned towards the reception of an allogeneic fetus. What is known already : NK cells are important for successful pregnancy. After implantation, NK cells encounter extravillous trophoblast cells and regulate trophoblast invasion. NK cell activity is amongst others regulated by C-type lectin heterodimer (CD94/NKG2) and killer cell immunoglobulin-like (KIR) receptors. KIR expression on decidual NK cells is affected by the presence of maternal HLA-C and biased towards KIR2D expression. However, little is known about NKR expression on eNK cells prior to pregnancy. Study design size , Duration: In this study, matched peripheral and menstrual blood (a source of endometrial cells) was obtained from 25 healthy females with regular menstrual cycles. Menstrual blood was collected during the fi rst 36 h of menstruation using a menstrual cup, a non-invasive technique to obtain endometrial cells. Participants / materials , setting , methods : KIR and NKG2 receptor expression on eNK cells was characterized by 10- color fl ow cytometry, and compared to matched pbNK cells of the same female. KIR and HLA-C genotypes were determined by PCR-SSOP techniques. Anti-CMV IgG antibodies in plasma were measured by chemiluminescence immunoassay. Main results and the role of chance : KIR expression patterns of eNK cells collected from the same female do not differ over consecutive menstrual cycles. The percentage of NK cells expressing KIR2DL2/L3/S2, KIR2DL3, KIR2DL1, LILRB1 and/or NKG2A was signi fi cantly higher in eNK cells compared to pbNK cells, while no signi fi cant difference was observed for NKG2C, KIR2DL1/S1, and KIR3DL1. The NKR repertoire of eNK cells was clearly different from pbNK cells, with eNK cells co-expressing more than three NKR simul- taneously. In addition, outlier analysis revealed 8 and 15 NKR subpopulation expansions in eNK and pbNK cells, respectively. In contrast to the pbNK cell population, the expansions present in the eNK cell population were independent of CMV status and HLA-C genotype. Moreover, the typical NKG2C imprint induced by CMV infection on pbNK cells was not observed on eNK cells from the same female, sug- gesting a rapid local turnover of eNK cells and/or a distinct licensing process. Limitations reasons for caution : Based on our previous work and the parameters studied here, menstrual blood-derived eNK cells closely resemble biopsy-derived eNK cells. However, sampling is not done at the exact same time during the menstrual cycle, and therefore we cannot exclude some, as yet undetected, differences. Wider implications of the findings : Our data reveals that NK cells in the pre-implantation endometrium appear to have a dedicated tissue-speci fi c phenotype, different from NK cells in peripheral blood. This may indicate that eNK cells are fi nely tuned to receive an allogeneic fetus. Studying the endometrial NKR repertoire of women with pregnancy related problems could provide clues to understand the pathogenesis of pregnancy complications. Study funding / competing interest ( S ): No external funding was obtained for the present study. None of the authors has any conflict of interest to declare.
Keywords		menstrual blood NK cells endometrium menstrualna kri NK celice endometrij