Characterization of dendritic cell (DC)-10 in recurrent miscarriage and recurrent implantation failure

in Reproduction
Correspondence should be addressed to Y Zeng; Email: zengyong1966@gmail.com

*(S Liu and H Wei contributed equally to this work)

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During pregnancy, the maternal immune system must tolerate the persistence of semi-allogeneic fetus in the maternal tissue. Inadequate recognition of fetal antigens may lead to pregnancy complications, such as recurrent miscarriage (RM) and recurrent implantation failure (RIF). Dendritic cells (DCs) are key regulators of protective immune responses and the development and maintenance of tolerance. Regarding that DCs are important in the establishment of immune tolerance in human pregnancy, it would be important to study the microenvironment in which DCs reside or are activated may affect their functions toward tolerance rather than active immune response. IL-10 plays a critical role in the maintenance of normal pregnancy, and the increased production of IL-10 is associated with successful pregnancy. In this study, we provide an in-depth comparison of the phenotype and cytokine production by DC-10 and other DC subsets, such as iDC and mDC. CD14+ monocyte-derived DCs were differentiated in the presence of IL-10 (DC-10) in vitro from ten normal fertile controls, six RM women and seven RIF women, and characterized for relevant markers. DC-10 was characterized by relatively low expression of costimulatory molecule CD86, as well as MHC class II molecule HLA-DR, high expression of tolerance molecules HLA-G, ILT2, ILT4 and immunosuppressive cytokine IL-10, but produced little or no proinflammatory cytokines, such as TNF-α, IL-6 and IL-12p70. Our study provides a better understanding of the phenotypical properties of DC-10, which may participate in the complex orchestration that leads to maternal immune tolerance and homeostatic environment in human pregnancy.

Downloadable materials

  • Supplementary Table 1. Comparison of phenotype and tolerance molecules expression of iDC, mDC and DC-10 among control, RM and RIF groups.
  • Supplementary Table 2. Comparison of cytokine production of iDC, mDC and DC-10 among control, RM and RIF groups.

 

    Society for Reproduction and Fertility

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    Phenotype of DC-10. (A) Histograms of the different markers on different DC subpopulations are shown as open graphs, with matched isotype controls in gray. Three representative donors of six independent controls, ten independent patients with RM and seven independent patients with RIF analyzed are presented, respectively. (B) The mean fluorescence intensity (MFI; mean ± s.e.m.) is corrected for the MFI of matched isotype controls, and corrected MFI is shown. *P < 0.05, **P < 0.01, ***P < 0.001 when the data were analyzed by Kruskal–Wallis test followed by a pairwise multiple comparison procedure.

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    Tolerance molecules expressed by DC-10. (A) Histograms of the different tolerogenic markers HLA-G, ILT2 and ILT4 on different DC subpopulations are shown as open graphs, with matched isotype controls in gray. Three representative donors of six independent controls, ten independent patients with RM and seven independent patients with RIF analyzed are presented, respectively. (B) The mean fluorescence intensity (MFI; mean ± s.e.m.) is corrected for the MFI of matched isotype controls, and corrected MFI is shown. *P < 0.05, **P < 0.01, ***P < 0.001 when the data were analyzed by Kruskal–Wallis test followed by a pairwise multiple comparison procedure.

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    Cytokine production by DC-10. Supernatants were collected and TNF-α, IL-6, IL-10 and IL-12p70 production by different DC subpopulations were determined by LEGENDplex. The mean ± s.e.m. levels of cytokines detected in four independent controls, four independent RM patients and four independent RIF patients are presented. *P < 0.05, **P < 0.01 when the data were analyzed by Kruskal–Wallis test followed by a pairwise multiple comparison procedure.

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