Uterine NK cells are critical in shaping DC immunogenic functions compatible with pregnancy progression.
Dendritic cell (DC) and natural killer (NK) cell interactions are important for the regulation of innate and adaptive immunity, but their relevance during early pregnancy remains elusive. Using two different strategies to manipulate the frequency of NK cells and DC during gestation, we investigated their relative impact on the decidualization process and on angiogenic responses that characterize murine implantation. Manipulation of the frequency of NK cells, DC or both lead to a defective decidual response characterized by decreased proliferation and differentiation of stromal cells. Whereas no detrimental effects were evident upon expansion of DC, NK cell ablation in such expanded DC mice severely compromised decidual development and led to early pregnancy loss. Pregnancy failure in these mice was associated with an unbalanced production of anti-angiogenic signals and most notably, with increased expression of genes related to inflammation and immunogenic activation of DC. Thus, NK cells appear to play an important role counteracting potential anomalies raised by DC expansion and overactivity in the decidua, becoming critical for normal pregnancy progression.
Irene
I
Tirado-González
Medicine University of Berlin, Charité Centre 12 Internal Medicine and Dermatology, Laboratory of Reproductive Medicine, Berlin, Germany.
Irene Tirado
IT
González
Gabriela
G
Barrientos
Nancy
N
Freitag
Teresa
T
Otto
Victor L J L
VL
Thijssen
Petra
P
Moschansky
Petra
P
von Kwiatkowski
Burghard F
BF
Klapp
Elke
E
Winterhager
Stefan
S
Bauersachs
Sandra M
SM
Blois
D000818:Animals; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007150:Immunohistochemistry; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014599:Uterus / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*