Human umbilical cord mesenchymal stem cells confer potent immunosuppressive effects in Sjögren’s syndrome by inducing regulatory T cells

Abstract

Background Primary Sjögren’s syndrome (SS) is a lymphoproliferative disease with a chronic autoimmune disorder characterized by mononuclear cell (MNC) infiltration of notably the lacrimal and salivary glands. As mesenchymal stem cells (MSCs) regulate series of immunological responses partially by regulating proportion of CD4+ T cells and inducing an immunosuppressive local milieu, umbilical cord MSCs (UC-MSCs) are being considered as a novel source for cell-based therapies against primary SS. This study aimed to investigate the feasibility of UC-MSCs in treatment of SS and to explore the possible mechanism(s) with the special emphasis on regulatory T cells (Tregs). Methods Potent immunosuppressive effects of human UC-MSCs on SS were explored in vivo and in vitro. To study the effects of human UC-MSCs on the development and progression of SS, human UC-MSCs were administered before disease onset (preventive protocol) and after disease occurrence (therapeutic protocol) in non-obese diabetic (NOD) mice. In human study, the effect of human UC-MSCs on T cells from SS patients was studied. Results In both protocols, the histopathology of submandibular and sublingual salivary glands showed decreased inflammatory infiltrates. In vitro, human UC-MSCs exhibited potent suppressive effects on responses of MNCs in NOD mice and T cells in SS patients. Such inhibitory effects were coupled with decreased production of proinflammtory cytokines interferon-γ, interleukin (IL)-6, tumor necrosis factor-α and increased production of IL-10 (n = 10, p < .01). The frequency of CD4+Foxp3+T cells in the spleen of NOD recipients was elevated (n = 6, p < .05). Conclusion Human UC-MSCs are capable of inducing CD4+Foxp3+ T cells in both NOD mice and human in vitro. Human UC-MSCs effectively interfere with the autoimmune attack in the course of SS by inducing an in vivo state of T cell unresponsiveness and the upregulation of Tregs.