Abstract
BackgroundMesenchymal stem cells (MSCs) have been demonstrated to be effective in treating autoimmune diseases including Sjögren’s syndrome (SS). We aim to compare the effects of MSC transplantation (MSCT) and the role of serum interleukin-12 (IL-12) in SS.MethodsIL-12 levels were measured by ELISA. IL-12 mRNA transcripts in dendritic cells (DCs) were determined by RT-PCR. After co-culturing with MSCs, IL-12 mRNA transcripts in mouse and human DCs were detected. Non-obese diabetic (NOD) mice received MSCT, recombinant IL-12, or anti-IL-12 mAb treatment, respectively. Then, salivary flow rates, histopathology of salivary glands, and splenic lymphocyte subsets were examined in these mice.ResultsIL-12 levels in the serum were significantly increased in SS patients and positively correlated with the EULAR 2010 Sjögren’s syndrome disease activity index. DCs from SS patients produced more IL-12 than those from the control. Likewise, IL-12 treatment in NOD mice significantly decreased salivary flow rates and promoted lymphocyte infiltration in salivary glands. IL-12 antibodies downregulated Th1, Th17, and Tfh cell. MSCT enhanced salivary flow rates and decreased lymphocyte infiltrations in salivary glands of NOD mice. MSCT downregulated Th17 and Tfh cells but upregulated regulatory T cells. MSCT reduced IL-12 productions in both SS patients and mice.ConclusionOur results indicate that MSCs ameliorate SS possibly via suppressing IL-12 production in DCs and that IL-12 could be a potential therapeutic target of SS.Trial registrationNTC00953485. Registered June 2009.
Highlights
Mesenchymal stem cells (MSCs) have been demonstrated to be effective in treating autoimmune diseases including Sjögren’s syndrome (SS)
IL-12 levels did not correlate with SSA or SSB antibodies in the SS patients (Additional file 1: Figure S1)
Saliva flow rates were comparable between the IL-12 antibody and phosphate-buffered saline (PBS) treatment group (Fig. 4a), we found milder inflammatory infiltrates in the submandibular glands of IL-12 antibody-treated mice (Fig. 4b)
Summary
Mesenchymal stem cells (MSCs) have been demonstrated to be effective in treating autoimmune diseases including Sjögren’s syndrome (SS). Mesenchymal stem cells (MSCs), derived from either the bone marrow (BMMSCs), umbilical cord (UCMSCs), or adipose tissues (ADMSCs), have been shown to be effective in treating various autoimmune diseases, including systemic lupus erythematosis (SLE), rheumatoid. Shi et al Stem Cell Research & Therapy (2018) 9:308 glucocorticoid or glucocorticoid combined with immunosuppressive drugs could benefit from UCMSC transplantation [8]. These data provide strong evidences for the advantages of MSCT application in treating SS patients. Apart from inflammatory infiltrates in salivary glands, Sjögren’s syndrome is a disease with lymphocytic proliferation disorders. We aimed to study the effects and mechanisms of IL-12 on SS focusing on the local infiltrates and changes of lymphocyte subsets
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