Human decidua mesenchymal stem cells regulate decidual natural killer cell function via interactions between collagen and leukocyte-associated immunoglobulin-like receptor 1

The development of maternal tolerance to the fetal allograft in critical for the maintenance of the pregnancy, and it is accompanied by the development of a special decidual natural killer (dNK) cell tolerance phenotype. To understand the factors that influence dNK cells during early pregnancy, the present study aimed to identify mesenchymal stem cells (MSCs) from human first-trimester deciduas, termed decidual MSCs (DMSCs), and to investigate the effect of DMSCs on the regulation of dNK cells via collagen. Decidual samples were collected from women with normal pregnancy that had undergone elective vaginal surgical terminations at 6-9 weeks gestation. DMSCs derived from human decidual tissues were cultured under differentiation conditions to examine their multipotent differentiation capacities, and the expression of MSC-specific markers, including cluster of differentiation (CD) 44, CD73, CD105, CD90, CD34, CD31, CD14, CD45, CD11b and human leukocyte antigen-antigen D related, was determined. dNK cells were co-cultured with DMSCs in order to examine the effect of DMSCs on the tolerance phenotype of dNK cells. The expression of cell surface molecules, natural cytotoxicity triggering receptor 3 and killer cell immunoglobulin-like receptor (KIR) 2DL1, and the secretion of cytokines, including interferon-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-10, IL-4 and perforin, were examined by flow cytometry analysis. To determine whether the regulation of dNK cells by DMSCs was mediated by collagen, DMSCs were pre-treated with human recombinant leukocyte-associated immunoglobulin-like receptor (LAIR)-2 and transfected with pScoR-GFP-hP4H to inhibit the interaction between LAIR-1 and collagen. The present results demonstrated that collagen produced by DMSCs increased the expression of KIR2DL1 and IL-4, decrease the expression of NKp30 and TNF-alpha. In conclusion, the results of the present study demonstrated that DMSCs may be cultured in vitro for prolonged periods, whilst retaining the ability to differentiate into different cell lineages. In addition, DMSCs may modulate the function of dNK cells via the interaction between collagen and LAIR-1.