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Blood, 15 March 2008, Vol. 111, No. 6, pp. 3108-3115. Prepublished online as a Blood First Edition Paper on January 10, 2008; DOI 10.1182/blood-2007-08-105965.
Submitted August 7, 2007
Department of Experimental Medicine, University of Rome "La Sapienza", Rome, Italy * Corresponding author; email: angela.gismondi{at}uniroma1.it.
During early pregnancy, uterine mucosa decidualization is accompanied by a drastical enrichment of CD56highCD16negative NK cells. Decidual NK (dNK) cells differ from peripheral blood NK (pbNK) cells in several ways, but their origin is still unclear. Our results demonstrate that chemokines present in the uterus can support pbNK cell migration through human endothelial and stromal decidual cells. Notably, we observed that pregnant women pbNK cells are endowed with higher migratory ability with respect to non-pregnant women or male donor pbNK cells. Moreover, NK cell migration through decidual stromal cells was increased when progesterone-cultured stromal cells were used as substrate, and this correlated with the ability of progesterone to up-regulate stromal cell chemokine expression. Furthermore, we demonstrate that also dNK cells can migrate through stromal cells using a distinct pattern of chemokines. Finally, we found that pbNK cells acquire a chemokine receptor pattern very similar to that of dNK cells when contact decidual stromal cells. Collectively these results strongly suggest that pbNK cell recruitment to the uterus contributes to the accumulation of NK cells during early pregnancy; that progesterone plays a crucial role in this event; and that pbNK cells undergo reprogramming their chemokine receptor profile once exposed to uterine microenvironment.
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