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Departments of
*
Microbiology and Immunology and
Physiology, Dartmouth Medical School, Lebanon, NH 03756
Uterine NK (uNK) cells express a unique set of markers compared with blood NK cells. However, recent studies suggest that uNK cells may be derived from the recruitment of blood NK cells into the endometrium. In this study, we used an in vitro organ culture system to demonstrate that estradiol induces expression of chemokines CXCL10 and/or CXCL11 within human endometrium in 85% of patient samples tested. The average increase in gene expression after 10–9 M estradiol treatment was 8.5-fold for CXCL10 and 7.7-fold for CXCL11 compared with medium alone. We observed that a specific estrogen receptor antagonist (ICI182780) was able to prevent chemokine gene induction, indicating that the effect of estradiol was receptor mediated. Moreover, our study showed that progesterone induced CXCL10 and CXCL11 expression in 83% of endometrial samples tested. We have also found that uNK cells and blood NK cells express the receptor for CXCL10 and CXCL11, CXCR3, with the highest expression found on uNK cells and CD56bright blood NK cells. These data indicate that sex hormones induce specific chemokines in nonpregnant human endometrium that can activate NK cell migration, and suggest that this mechanism may account for the increased NK cell numbers in endometrium during the menstrual cycle.
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 C. Carlino, H. Stabile, S. Morrone, R. Bulla, A. Soriani, C. Agostinis, F. Bossi, C. Mocci, F. Sarazani, F. Tedesco, et al. Recruitment of circulating NK cells through decidual tissues: a possible mechanism controlling NK cell accumulation in the uterus during early pregnancy Blood, March 15, 2008; 111(6): 3108 - 3115. [Abstract] [Full Text] [PDF]
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 J. Szekeres-Bartho and J. Balasch Progestagen therapy for recurrent miscarriage Hum. Reprod. Update, January 1, 2008; 14(1): 27 - 35. [Abstract] [Full Text] [PDF]
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 D. B. Keskin, D. S. J. Allan, B. Rybalov, M. M. Andzelm, J. N. H. Stern, H. D. Kopcow, L. A. Koopman, and J. L. Strominger TGFbeta promotes conversion of CD16+ peripheral blood NK cells into CD16- NK cells with similarities to decidual NK cells PNAS, February 27, 2007; 104(9): 3378 - 3383. [Abstract] [Full Text] [PDF]
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Y. Hirota, Y. Osuga, K. Koga, O. Yoshino, T. Hirata, C. Morimoto, M. Harada, Y. Takemura, E. Nose, T. Yano, et al. The Expression and Possible Roles of Chemokine CXCL11 and Its Receptor CXCR3 in the Human Endometrium J. Immunol., December 15, 2006; 177(12): 8813 - 8821. [Abstract] [Full Text] [PDF]
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J. Hanna, H. Mussaffi, G. Steuer, S. Hanna, M. Deeb, H. Blau, T. I. Arnon, N. Weizman, and O. Mandelboim Functional aberrant expression of CCR2 receptor on chronically activated NK cells in patients with TAP-2 deficiency Blood, November 15, 2005; 106(10): 3465 - 3473. [Abstract] [Full Text] [PDF]
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X. Wu, L.-P. Jin, M.-M. Yuan, Y. Zhu, M.-Y. Wang, and D.-J. Li Human First-Trimester Trophoblast Cells Recruit CD56brightCD16- NK Cells into Decidua by Way of Expressing and Secreting of CXCL12/Stromal Cell-Derived Factor 1 J. Immunol., July 1, 2005; 175(1): 61 - 68. [Abstract] [Full Text] [PDF]
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