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TLR3-Involved Modulation of Pregnancy Tolerance in Double-Stranded RNA-Stimulated NOD/SCID Mice¹

Key Laboratory of Ministry of Education for Tissue Transplantation and Immunology, College of Life Science and Technology, Jinan University, Guangzhou City, China

This study aims to extend understanding of the relationship between TLR3-involved cell signaling and dsRNA-induced embryo resorption. Upon stimulation of dsRNA, the resorption rate of embryos was boosted dramatically in syngeneic mating BALB/c mice, but not significantly influenced in syngeneic mating NOD/SCID mice. Accordingly, there was an enhanced cell surface expression of TLR3 on placental CD45⁺ cells derived from BALB/c mice, concomitant with both increased percentages of CD45⁺CD80⁺ cells and CD8⁺CD80⁺ cells in flow cytometric analysis. In addition, both increased IL-2 and decreased IL-10 expression could be observed in CD45⁺ cell group in the intracellular detection by flow cytometry. In contrast, no such trends were observed in NOD/SCID model, and its resorption rate of embryos was kept at a low level throughout pregnancy. Neutralizing Abs against TLR3 could abrogate the embryo rejection induced by dsRNA in BALB/c mice, and simultaneously could reduce the CD80⁺ percentage in the CD45⁺ cell group. These results indicate that the interaction between dsRNA and TLR3 may be involved in the mobilization of CD45⁺CD80⁺ and CD8⁺CD80⁺ cells, followed by the up-regulation of IL-2 and down-regulation of IL-10 expression at the feto-maternal interface, and finally resulting in embryo rejection. The relatively low responsiveness of NOD/SCID mice may be one of the reasons why these mice appeared to be resistant to dsRNA-induced embryo resorption.

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The JI 2006 176: 3851-3852. [Full Text]  

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