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Regulatory T cells decrease invariant natural killer T cell-mediated pregnancy loss in mice

Mucosal Immunology, ISSN: 1933-0219, Vol: 10, Issue: 3, Page: 613-623
2017
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Beyond Immune Balance: The Pivotal Role of Decidual Regulatory T Cells in Unexplained Recurrent Spontaneous Abortion

Introduction Immune self-stabilization is one of the three functions of human immune system.1 Regulatory T (Treg) cells are named for their powerful function in regulating

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Pregnancy loss is the commonest complication of pregnancy. The causes of pregnancy loss are poorly understood. It has been reported that stimulation of invariant natural killer T (iNKT) cells using α-galactosylceramide (αGC) induces pregnancy loss in mice. Here we investigated the mechanisms, especially the role of regulatory T (Treg) cells, in iNKT cell-mediated pregnancy loss. We found that injection of αGC rapidly induced fetal resorption, activated decidual iNKT cells, decreased the percentage of decidual Treg cells and their interleukin (IL)-10 and transforming growth factor (TGF)-β production, and upregulated the levels of interferon (IFN)-γ, tumor necrosis factor-α, IL-4, and IL-10 in serum. Adoptive transfer of iNKT cells from wild-type (WT) and IL-4 −/− mice but not IFN-γ −/− mice into αGC-treated iNKT cell-deficient Jα18 −/− mice restored αGC-induced pregnancy loss. Adoptive transfer of Treg cells downregulated α-GC-induced pregnancy loss in WT mice. Finally, co-culture with αGC-stimulated decidual iNKT cells decreased the production of IL-10 and TGF-β in decidual Treg cells and inhibited their suppressive activity. These findings suggest that activation of iNKT cells induces pregnancy loss in mice in an IFN-γ-dependent manner. In addition, inhibition of the function of decidual Treg cells has an important role in iNKT cell-mediated pregnancy loss.

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