Journal of Reproductive Immunology 114 (2016) 10–17 Contents lists available at ScienceDirect Journal of Reproductive Immunology journal homepage: www.elsevier.com/locate/jreprimm Decidual soluble factors, through modulation of dendritic cells functions, determine the immune response patterns at the feto-maternal interface Hasan Namdar Ahmadabad a,b , Mojdeh Salehnia c , Shigeru Saito d , Seyed Mohammad Moazzeni a,∗ a Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran b Department of Pathobiology and Medical Laboratory Science, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran c Department of Anatomy, Faculty of Medical Sciences, Tehran, Iran d Department of Obstetrics and Gynecology, Graduate School of Medicine and Pharmaceutical Science for Research, University of Toyama,Toyama, Japan a r t i c l e i n f o Article history: Received 13 November 2015 Accepted 4 January 2016 Keywords: Abortion Decidua Dendritic cell Lymphocyte a b s t r a c t Dendritic cells (DCs) can acquire immunogenic or tolerogenic properties depending on intrinsic and tissue environmental factors. We aimed to determine the immunomodulatory effects of decidual soluble factors from abortion- and non-abortion-prone mice on DC functions. The decidual cell supernatants (DS) were obtained from abortion-prone and non-abortion-prone mice. Splenic DCs were treated with DS and conalbumin (as an antigen) and injected into the palms of the mice. After five days, regional lymph node cells were collected and cultured in the presence and absence of conalbumin. The proliferation of lymphocyte cells, the frequency of regulatory T cells (Tregs), and the production of IL-4 and IFN-  were measured by [ 3 H]thymidine incorporation, flow cytometry, and ELISA respectively. Our results indicated that DS from both abortion- and non-abortion-prone mice decreased the ability of DCs to induce lymphocyte proliferation and IFN- production, while enhanced their capacity to induce Tregs compared with non-treated DCs. Another important finding was that the immunosuppressive effects of DS from abortion-prone mice on DCs for inducing proliferative responses, developing Tregs, and producing IFN- by primed lymphocytes was less than DS from non-abortion-prone mice. We also found that only DS from non-abortion-prone mice could enhance the capacity of DCs to induce IL-4 production by primed lymphocytes. It can be concluded that decidua-secreted factors, by altering DC functions, can determine the pattern of immune responses at the fetomaternal interface and, subsequently, pregnancy outcome. © 2016 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Many different mechanisms acting locally or at a distance ensure tolerance of the semi-allogeneic fetus by the maternal innate and adaptive immune defenses (Koch and Platt, 2003). In contrast to this tolerance, some mechanisms exist that ensure the rejection of the fetus by the mother (spontaneous abortion) through the fail- ure of one or more tolerance induction mechanisms. It has been proposed that local immunoregulatory factors present at the feto- maternal interface help to maintain fetal tolerance (Guleria and Sayegh, 2007). In other words, the pattern of immune responses in decidua, as a fetal-independent tissue, plays a decisive role in ∗ *Corresponding author: Tel.: +98 2182883846; Fax: +98 21 82883846. E-mail address: moazzeni@modares.ac.ir (S.M. Moazzeni). maintaining tolerance to the semi-allogeneic fetus. The status of immunity of the decidua is characterized by the present cell types and the soluble factors produced therein. Immune cells represent a large component of decidual tissue and are composed of nat- ural killer cells (NK), macrophages, T lymphocytes, natural killer T (NKT) cells, regulatory T cells (Tregs), and dendritic cells (DCs) (Sanguansermsri and Pongcharoen, 2008). Dendritic cells are the most potent professional antigen- presenting cells (APCs), which serve as key regulators of immunological mechanisms and, depending on their subsets, may induce immunity or immunological tolerance. The activation of naive T cells, the regulation of T helper (TH) TH1/TH2 development (Moser and Murphy, 2000), and the generation of Tregs (Hu and Wan, 2011) are considered the unique abilities of DCs. Decidual DCs have been known to be key players in the initiation and regulation of immune responses at the fetomaternal inter- http://dx.doi.org/10.1016/j.jri.2016.01.001 0165-0378/© 2016 Elsevier Ireland Ltd. All rights reserved.