TLR3-involved modulation of pregnancy tolerance in double-stranded RNA-stimulated NOD/SCID mice.
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 CD8alpha(+)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 CD8alpha(+)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.
Key Laboratory of Ministry of Education for Tissue Transplantation and Immunology, College of Life Science and Technology, Jinan University, Guangzhou City, China. yilinonline@gmail.com
Yi
Y
Lin
Zhenhong
Z
Liang
Yijing
Y
Chen
Yaoying
Y
Zeng
D000375:Aging / Q000276:immunology; D000818:Animals; D000906:Antibodies / Q000276:immunology; D018122:B7-1 Antigen / Q000378:metabolism; D020964:Embryo Loss / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology*; D007376:Interleukin-2 / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy / Q000276:immunology*; D012330:RNA, Double-Stranded / Q000276:immunology* / Q000494:pharmacology; D013154:Spleen / Q000378:metabolism; D051196:Toll-Like Receptor 3 / Q000276:immunology* / Q000378:metabolism
D000906:Antibodies; D018122:B7-1 Antigen; D007376:Interleukin-2; D012330:RNA, Double-Stranded; D051196:Toll-Like Receptor 3; D017493:Leukocyte Common Antigens