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 (dNK) 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 (DSCs) on dNKs.

RESULTS

Maternal-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.

CONCLUSION

Trophoblasts and DSCs regulate decidual NK cell functions via secreting collagen, which is involved in the maintenance of human pregnancy.