TY - JOUR
T1 - NK cell-derived IL-10 is critical for DC-NK cell dialogue at the maternal-fetal interface
AU - Blois, Sandra M.
AU - Freitag, Nancy
AU - Tirado-González, Irene
AU - Cheng, Shi Bin
AU - Heimesaat, Markus M.
AU - Bereswill, Stefan
AU - Rose, Matthias
AU - Conrad, Melanie L.
AU - Barrientos, Gabriela
AU - Sharma, Surendra
N1 - Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - DC-NK cell interactions are thought to influence the development of maternal tolerance and de novo angiogenesis during early gestation. However, it is unclear which mechanism ensures the cooperative dialogue between DC and NK cells at the feto-maternal interface. In this article, we show that uterine NK cells are the key source of IL-10 that is required to regulate DC phenotype and pregnancy success. Upon in vivo expansion of DC during early gestation, NK cells expressed increased levels of IL-10. Exogenous administration of IL-10 was sufficient to overcome early pregnancy failure in dams treated to achieve simultaneous DC expansion and NK cell depletion. Remarkably, DC expansion in IL-10-/- dams provoked pregnancy loss, which could be abrogated by the adoptive transfer of IL-10+/+ NK cells and not by IL-10-/- NK cells. Furthermore, the IL-10 expressing NK cells markedly enhanced angiogenic responses and placental development in DC expanded IL-10-/- dams. Thus, the capacity of NK cells to secrete IL-10 plays a unique role facilitating the DC-NK cell dialogue during the establishment of a healthy gestation.
AB - DC-NK cell interactions are thought to influence the development of maternal tolerance and de novo angiogenesis during early gestation. However, it is unclear which mechanism ensures the cooperative dialogue between DC and NK cells at the feto-maternal interface. In this article, we show that uterine NK cells are the key source of IL-10 that is required to regulate DC phenotype and pregnancy success. Upon in vivo expansion of DC during early gestation, NK cells expressed increased levels of IL-10. Exogenous administration of IL-10 was sufficient to overcome early pregnancy failure in dams treated to achieve simultaneous DC expansion and NK cell depletion. Remarkably, DC expansion in IL-10-/- dams provoked pregnancy loss, which could be abrogated by the adoptive transfer of IL-10+/+ NK cells and not by IL-10-/- NK cells. Furthermore, the IL-10 expressing NK cells markedly enhanced angiogenic responses and placental development in DC expanded IL-10-/- dams. Thus, the capacity of NK cells to secrete IL-10 plays a unique role facilitating the DC-NK cell dialogue during the establishment of a healthy gestation.
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U2 - 10.1038/s41598-017-02333-8
DO - 10.1038/s41598-017-02333-8
M3 - Article
C2 - 28526846
AN - SCOPUS:85019884636
SN - 2045-2322
VL - 7
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 2189
ER -