Trophoblasts and decidual stromal cells regulate decidual NK cell functions via interaction between collagen and LAIR-1

Am J Reprod Immunol. 2014 Apr;71(4):368-78. doi: 10.1111/aji.12211. Epub 2014 Feb 18.


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.

Keywords: Collagen; LAIR-1; Th1/Th2; decidual NK cell; maternal-fetal interface.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abortion, Spontaneous
  • Cells, Cultured
  • Coculture Techniques
  • Collagen / biosynthesis
  • Collagen / genetics
  • Collagen / immunology*
  • Decidua / cytology*
  • Female
  • Humans
  • Killer Cells, Natural / cytology*
  • Pregnancy
  • RNA Interference
  • RNA, Small Interfering
  • Receptors, Immunologic / antagonists & inhibitors
  • Receptors, Immunologic / biosynthesis
  • Receptors, Immunologic / immunology*
  • Receptors, Immunologic / metabolism
  • Stromal Cells / cytology
  • Trophoblasts / cytology*


  • LAIR-2 receptor
  • RNA, Small Interfering
  • Receptors, Immunologic
  • leukocyte-associated immunoglobulin-like receptor 1
  • Collagen