title: Regulatory T cells decrease invariant natural killer T cell-mediated pregnancy loss in mice.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynecology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China.
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China.
authors.forename: J
authors.initials: J
authors.lastname: Tu
authors.affiliation: Department of Obstetrics and Gynecology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Obstetrics, Gynecology and Women's Health, University of Missouri School of Medicine, Columbia, Missouri, USA.
authors.forename: J
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Obstetrics, Gynecology and Women's Health, University of Missouri School of Medicine, Columbia, Missouri, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Schust
mesh_terms: D000022:Abortion, Spontaneous / Q000276:immunology*; D019264:Adoptive Transfer; D000818:Animals; D002478:Cells, Cultured; D018920:Coculture Techniques; D003656:Decidua / Q000276:immunology*; D005260:Female; D005699:Galactosylceramides / Q000276:immunology*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology*; D011247:Pregnancy; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D005699:Galactosylceramides; C493154:alpha-galactosylceramide; D015847:Interleukin-4; D007371:Interferon-gamma