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

ProblemTo determine the effect of collagen from maternal-fetal interface on decidual natural killer cell (dNK) function. Method of studyDecidual 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 (DSCs) on dNKs. ResultsMaternal-fetal interface of normal pregnancy showed higher collagen and LAIR-1 expression than that of miscarriage. Co-culture of dNKs with HTR-8/DSCs up-regulated LAIR-1 on dNKs 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 dNKs. Co-culture of dNKs with HTR-8/DSCs decreased perforin expression and Th1-type cytokines production by dNKs, which could be abrogated by LAIR-2. In addition, silence of collagen in HTR-8/DSCs by shRNA significantly attenuated regulation on dNKs. ConclusionTrophoblasts and DSCs regulate decidual NK cell functions via secreting collagen, which is involved in the maintenance of human pregnancy.