Trophoblasts and Decidual Stromal Cells Regulate Decidual NK Cell Functions Via Interaction between Collagen and LAIR‐1

Problem To determine the effect of collagen from maternal–fetal interface on decidual natural killer cell (d NK ) function. Method of study Decidual and villous samples were collected from normal pregnancy and miscarriage. The phenotype and cytokine production were analyzed, respectively, by flow cytometry and enzyme‐linked immunosorbent assay ( ELISA ). Co‐culture was established to investigate the effect of trophoblasts and decidual stromal cells ( DSC s) on d NK s. Results Maternal–fetal interface of normal pregnancy showed higher collagen and LAIR ‐1 expression than that of miscarriage. Co‐culture of d NK s with HTR ‐8/ DSC s up‐regulated LAIR ‐1 on d NK s that could be attenuated by pre‐treatment with LAIR ‐2, a competitive inhibitor of LAIR ‐1. Collagen down‐regulated expression of cell surface receptor activity and intracellular perforin, while it up‐regulated expression of suppressive receptor on d NK s. Co‐culture of d NK s with HTR ‐8/ DSC s decreased perforin expression and T h1‐type cytokines production by d NK s, which could be abrogated by LAIR ‐2. In addition, silence of collagen in HTR ‐8/ DSC s by sh RNA significantly attenuated regulation on d NK s. Conclusion Trophoblasts and DSC s regulate decidual NK cell functions via secreting collagen, which is involved in the maintenance of human pregnancy.