Recruitment of circulating NK cells through decidual tissues: a possible mechanism controlling NK cell accumulation in the uterus during early pregnancy.
During early pregnancy, uterine mucosa decidualization is accompanied by a drastic enrichment of CD56(high)CD16(-) natural killer (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's pbNK cells are endowed with higher migratory ability compared with nonpregnant women's or male donors' 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 dNK cells migrate through stromal cells using a distinct pattern of chemokines. Finally, we found that pbNK cells acquire a chemokine receptor pattern similar to that of dNK cells when they 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 of their chemokine receptor profile once exposed to uterine microenvironment.
Carlino
Claudia
C
Department of Experimental Medicine, University La Sapienza, Rome, Italy.
Stabile
Helena
H
Morrone
Stefania
S
Bulla
Roberta
R
Soriani
Alessandra
A
Agostinis
Chiara
C
Bossi
Fleur
F
Mocci
Carlo
C
Sarazani
Filippo
F
Tedesco
Francesco
F
Santoni
Angela
A
Gismondi
Angela
A
D002465:Cell Movement; D002478:Cells, Cultured; D018925:Chemokines / Q000235:genetics; D018920:Coculture Techniques; D003656:Decidua / Q000166:cytology* / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology* / Q000378:metabolism; D008297:Male; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics; D019707:Receptors, Chemokine / Q000235:genetics; D017154:Stromal Cells / Q000378:metabolism; D013997:Time Factors
D018925:Chemokines; D012333:RNA, Messenger; D019707:Receptors, Chemokine