AB0130 Mesenchymal stem cells alleviate sle through promoting treg cells by hla-g. (15th June 2017)

• Record Type: Journal Article
• Authors: Chen, C; Liang, J; Yao, G; Zhang, Z; Huang, S; Sun, L
• Is Part Of: Annals of the rheumatic diseases. Volume 76(2017)Supplement 2
• Page Start: 1092
• Page End: 1092
• Publication Date: 2017-06-15
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2017-eular.3600
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: Soluble human leukocyte antigen-G (sHLA-G) is a non-classical HLA class I molecule, exhibiting strong immunosuppressive properties by inducing the differentiation of T regulatory cells (Treg). Mesenchymal stem cells (MSCs) transplantation alleviates disease progression in systemic lupus erythematosus (SLE) patients. However, the underlying mechanisms are largely unknown. Objectives: The aim of the present study is to explore whether sHLA-G is involved in upregulating Treg cells by MSCs, which contributes to therapeutic effects of MSCs transplantation in SLE. Methods: The serum sHLA-G levels of SLE patients and healthy controls were detected by ELISA. The percentages of peripheral blood CD4 + ILT2 +, CD8 + ILT2 +, CD19 + ILT2 + cells and Treg cells were determined by flow cytometry. Ten patients with active SLE, refractory to conventional therapies, were infused with MSCs and serum sHLA-G was measured 24 h after infusion. Peripheral blood mononuclear cells (PBMCs) were isolated from SLE patients and co-cultured with UC-MSCs for 3 days at different ratios (50:1, 10:1, and 2:1) with or without anti-HLA-G antibodies, and the frequencies of CD4 + CD25 + Foxp3 + T cells were then determined by flow cytometry. Results: The concentrations of serum sHLA-G were comparable between SLE patients and healthy controls. However, there was a negative correlation between sHLA-G levels and SLE disease activity index (SLEDAI) scores in active SLE patients (SLEDAI >4). We found that serum sHLA-G levels were negatively correlated with blood urea nitrogen, serum creatinine and 24-hour urine protein in SLE patients. The sHLA-G levels were significantly lower in SLE patients with renal involvement than those without renal involvement. The expression of ILT2 on CD4 + T cells from SLE patients decreased significantly compared to that of healthy controls. A positive correlation between the frequencies of Treg and CD4 + ILT2 + T cells was found in SLE patients. The levels of sHLA-G increased 24 h after UC-MSC transplantation. The frequencies of Treg cells and the expressions of ILT2 on CD4 + Tcells were significantly increased 24 h after transplantations. In vitro studies showed that MSCs increased the frequency of Treg cells in SLE patients in a dose-dependent manner, which was partly abrogated by the anti-HLA-G antibody. Conclusions: Our results suggested that MSCs might alleviate SLE through upregulating Treg cells, which was partly dependent on sHLA-G. Disclosure of Interest: None declared