NK cell-derived IL-10 is critical for DC-NK cell dialogue at the maternal-fetal interface

Sandra M. Blois, Nancy Freitag, Irene Tirado-González, Shi Bin Cheng, Markus M. Heimesaat, Stefan Bereswill, Matthias Rose, Melanie L. Conrad, Gabriela Barrientos, Surendra Sharma

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article number2189
JournalScientific reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017
Externally publishedYes

ASJC Scopus subject areas

  • General

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