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AB0143 Umbilical Cord Mesenchymal Stem Cells Increase Treg Cells via SHLA-G in Sle Patients
  1. C. Chen,
  2. J. Liang,
  3. W. Chen,
  4. L. Sun
  1. Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China

Abstract

Background Human leukocyte antigen-G (HLA-G) is a non-classical HLA class I molecule, exhibiting strong immunosuppressive properties by inducing the differentiation of regulatory T cells (Treg). Previous studies showed that umbilical cord mesenchymal stem cells (UCMSCs) transplantation could alleviate disease progression in SLE patients. However, the underlying mechanisms are largely unknown.

Objectives To explore whether sHLA-G was involved in upregulation effects of MSCs on Treg, which contribute to the immune torlerance during SLE.

Methods The level of sHLA-G was detected by ELISA in SLE patients and healthy controls. The correlations between the levels of sHLA-G and clinical features, percentages of HLA-G receptor ILT2 and Treg cells were analyzed by Sparman's correlation test respectively. The percentage of ILT2 on T and B lymphocytes was examined by flow cytometry. PBMC were isolated from SLE patients and co-cultured with UC-MSCs for 3 days at different ratios (50:1, 10:1, 2:1) with or without HLA-G antibodies, and then the frequencies of CD4+CD25+Foxp3+T cells were determined by flow cytometry.

Results The concentration of sHLA-G was increased in SLE patients compared with healthy control subjects (21.76 ng/mL ±1.206 VS 16.84 ng/mL ±1.656, p <0.05). However, there was a negative correlation between sHLA-G levels and SLEDAI scores in active SLE patients (SLEDAI >4). We found that sHLA-G levels were negative correlated with urea nitrogen, serum creatinine and 24-hour urine protein but positively correlated with platelet in SLE patients. What's more, the sHLA-G levels were significantly lower in SLE patients with renal involvement compared with those without renal involvement. The expression of ILT2 in CD4+ T cells from SLE patients decreased significantly compared to controls. A positive relationship between the frequency of Treg cells and CD4+ILT2+ T cells in SLE patients was found. The levels of sHLA-G increased 24 hours post MSCs transplantation. In vitro studies showed MSCs increased the frequency of Treg cells in SLE patients in a dose-dependent manner, which was partly abrogated by anti-HLA-G antibody.

Conclusions Our results suggested that UCMSCs could alleviate SLE through upregulating Treg cells partly dependent on sHLA-G.

Disclosure of Interest None declared

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