engleski

Mucin I tune cytolytic mediators expression in decidual CD56+ cells via decidual CD14+ cells

Problem: Mucin-1 (MUC-1) is a glycoprotein expressed and secreted from endometrial epithelial (surface or glandular) cells. It constitutes glycoprotein coat which is drastically reduced in the uterus of many species during the time of embryo implantation, since it acts as a barrier to implantation. Little is known about immunologic effects of MUC I within decidual tissue. The aim of our study was to investigate possible affects of MUC I on the function of decidual CD14+ antigen presenting cells. Design & methods: Decidual mononuclear cells (DMC) were obtained by enzymatic digestion and gradient density centrifugation. Binding assay using anti-CD206 monoclonal antibody (PAM-1 clone) or FITC-dextran uptake were performed in MUC I treated or untreated DMC in order to analyze CD14+ cell mediated functions. Cytokines: interleukin (IL)-10, IL-15, IL-18 and interferon gamma (IFN- ) were labeled in permeabilized MUC I treated or untreated CD14+ cells (18 hours). Decidual CD56+ cells were magnetically separated from non-adherent DMC fraction and CD14+ cells were enriched from adherent DMC fraction after the CD1a+ cell depletion. Cytolytic mediators: perforin, Fas ligand (FasL), tumor necrosis factor– related apoptosis-inducing ligand (TRAIL) and granulysin were detected in CD56+ cells after the co-culture with CD14+ cells at cell ratio 5:1 or after the culture in the medium only. Results: MUC I on a dose dependent manner reduced anti-CD206 monoclonal antibody ligation and FITC-dextran uptake by CD14+ cells from DMC suspension. The viability of CD14+ cells and the expression of CD80, CD86 and HLA-DR on their surface (percentage and mean fluorescence intensity-MFI) did not significantly change after 18 hours culture with MUC I (200  g/ml) in comparison to the cells cultured in the medium only. CD14+ cells recovered from DMC cultured in the presence of MUC I did not basically change IFN- and IL-10 intracellular expression, whereas percentage of IL-15 and IL-18 expressing CD14+ cells decreased in the suspension. Preliminary data show that TAG-72 treated CD14+ cells were unable to sustain perforin, FasL, TRAIL and granulysin expression in decidual CD56+ cells as untreated CD14+ cells did. Conclusion: MUC I binds and internalizes CD206 receptor and down-regulates IL-15 and IL-18 cytokines expression in decidual CD14+ cells leading to down-regulation of cytolytic mediator protein expression in surrounding decidual NK cells. Acknowledgement: We gratefully acknowledge the financial support provided by the Croatian Ministry of Science (Grants No. 0620402-0376, 0620402-0377 and 0620402-0379) and the EMBIC project, European FP6, NoE, LSHM-CT-2004-512040.

CD14+ cells; mucin I; CD56+ cells

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