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FRI0266 The mechanism of umbilical cord mesenchymal stem cells in the upregulation of regulatory t cells by tgf-b1 in systemic lupus erythematosus
  1. L. Sun1,
  2. L. Lu1,
  3. D. Wang1,
  4. X. Li1
  1. 1Department of Rheumatology and Immunology, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China


Objectives The aim of this study is to investigate the mechanism of umbilical cord mesenchymal stem cells (UC-MSC) in the upregulation of peripheral regulatory T cells in patients with systemic lupus erythematosus (SLE).

Methods Peripheral blood mononuclear cells (PBMC) from 20 SLE patients and normal controls were co-cultured with UC-MSC at different ratios respectively for 72 hours, and the proportions of CD4+CD25+Foxp3+regulatory T cells were analyzed by flow cytometry. PBMC and serum from active SLE patients and normal controls were used to stimulate UC-MSC, TGF-β1 mRNA expressions on UC-MSC were detected by real-time fluorescence quantitative polymerase chain reaction (real-time PCR). Supernatant TGF-β1 levels were determined by enzyme-linked immunesorbent assay (ELISA). The TGF-β1 small interfering RNA (siRNA) was used to interfere TGF-β1 expression on UC-MSC, then to determine its effect on the regulation of SLE Treg cells. TGF-β1 inhibitor was added in the culture system of UC-MSC and PBMC from active SLE patients, to observe its role on the upregulation of Treg cells by UC-MSC.

Results UC-MSC could dose-dependently upregulate peripheral CD4+CD25+Foxp3+Treg proportion in SLE patients, which was not depended on cell-cell contact. UC-MSC had no regulatory effect on Treg cells in normal controls. Compared with the non-stimulated group and normal PBMC stimulated group, PBMC from SLE patients significantly promoted TGF-β1 mRNA expression on UC-MSC (relative gene expression was 1.00 ± 0.09,1.95 ± 0.62,4.20 ± 2.34, respectively, both P<0.05). Supernatant TGF-β1 levels were significantly elevated in the presence of SLE PBMC. Serum of SLE patients (5%) enhanced TGF-β1mRNAexpression on UC-MSC (12.19 ± 4.49), significantly higher than fetal bovine serum cultured group (1.33 ± 0.06, P<0.01) and normal individuals serum cultured group (2.53 ± 0.72, P<0.01). Additionally, TGF-β1 siRNA interfered UC-MSC failed to upregulate Treg cells in SLE patients (SLE PBMC + TGF-β1siRNA UC-MSC group 2.33% ± 0.99% vs.SLE PBMC group 1.80%±0.65%, P>0.05). Furthermore, TGF-β1 specific inhibitor SB431542 significantly inhibited the regulatory role of UC-MSC on Treg cells in SLE patients (SLE PBMC+UC-MSC+SB431542 group 4.58%±2.10% vs. SLE PBMC+UC-MSC group 7.85%±3.54%, P<0.05).

Conclusions Immune microenvironment in SLE patients can significantly stimulate TGF-β1 expression on UC-MSC, which plays an important role in the upregulation of Treg cells in patients. This study provides a new mechanism for the regulation of Treg cells by UC-MSC and treatment for SLE patients.

Disclosure of Interest: None Declared

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