Background Mesenchymal stem cells (MSCs) have been demonstrated to be effective in treating clinical and experimental Sjogren's syndrome (SS). However, the underlying mechanisms of benefit effects of MSCs on pSS remain unclear. IL-12 was mainly generated from monocytes, dendritic cells (DCs) and macrophages, and regarded as a pro-inflammatory cytokine in autoimmune diseases, including SS.
Objectives In this study we test whether the therapeutic effects of MSCs on SS is mediated by reducing IL-12 production.
Methods 1×106 human umbilical cord derived MSCs were injected into NOD mice (experimental Sjogren's syndrome, ESS) via tail vein. 4 weeks later, the salivary flow rates were detected. Splenocytes were collected and CD11c+ and CD11b+ cells were sorted by magnetic beads. Lacrimal and salivary glands were collected for histologic analysis. Serum IL-12 was quantified by ELISA inprimary Sjogren's syndrome (pSS) patients and healthy controls. 5 patients with pSS received MSCs transplantations. Whole blood was collected before MSCs treatment and 4 weeks later. CD14+ cells from pSS patients and healthy controls were isolated by magnetic beads. The CD14+ cells were induced to generate DCs or macrophages. Expression of IL-12 was detected by RT-PCR. Human THP-1 cells were induced towards macrophage or DC. THP-1 cells, THP-1-induced macrophages and DCs were co-cultured with MSCs, respectively. IL-12 levels in supernatants were detected by ELISA. IL-12 gene expression was quantified by real-time PCR.
Results MSCs transplantation improved salivary flow rates and decreased lymphocyte infiltrations in lacrimal and salivary glands, proving its effectiveness in alleviating symptoms of NOD mice. In vivo transplantation of MSCs into NOD mice also reduced serum IL-12 levels, and IL-12 mRNA in CD11c+ and CD11b+ cells. Serum IL-12 levels were significantly increased in pSS patients. MSCs transplantation also decreased IL-12 levels in pSS patients after 4 weeks. CD14+ monocytes, monocyte-derived DCs and macrophages from pSS patients generated significantly more IL-12 than that from healthy individuals. MSCs significantly reduced IL-12 production by human THP-1-induced DCs, macrophages or monocytes in vitro. Moreover, MSCs also decreased IL-12 production in mouse Raw246.7 cells (mouse macrophage), mouse CD11c+ cells and CD11b+ cells in vitro.
Conclusions IL-12 over-production by APCs may contribute to the pathogenesis of pSS and ESS. MSCs may alleviate clinical and experimental Sjogren's syndrome through decreasing IL-12 production.
Disclosure of Interest None declared