• Darlan Dewi Masyithah DM Department of Parasitology, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia., Delfitri Munir, Agung Putra, and Jusuf Nelva Karmila NK Department of Dermatology and Venereology, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia..
• Department of Parasitology, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia.
• J Formos Med Assoc. 2021 Jan 1; 120 (1 Pt 3): 602-608.

Background/PurposeRegulatory T-cell (Treg) defects may cause autoreactivity of both T and B cells, leading to autoimmune disease including systemic lupus erythematosus (SLE). The immune response defects in SLE are characterized by the decreased expression of CD4, CD25, and Foxp3, known as inducible Treg (iTreg). Therefore, restoring iTreg expression can reverse autoimmunity states into immune tolerances leading to normal immune responses. Mesenchymal stem cells (MSCs) have immunomodulatory properties to control inflammatory milieu, including in SLE inflammation by releasing TGFβ1, IL10, and PGE2, thus MSCs can potentially generate iTreg cells. However, the mechanisms of MSC-released TGFβ1 to promote iTreg generation in human SLE remains unclear. This study aims to analyze the role of MSC-released TGFβ1 in generating CD4+, CD25+, and Foxp3+ expression in iTreg cells from human SLE peripheral blood mononuclear cells (PBMCs).MethodsThis study used a post-test control group design. MSCs were obtained from human umbilical cord blood and characterized according to their surface antigen expression and multilineage differentiation capacities. PBMCs isolated from SLE patients were divided into five groups, including sham, control, and three treatment groups. The treatment groups were treated by co-culturing MSCs to PBMCs with ratio of 1:1 (T1), 1:25 (T2), and 1:50 (T3) for 72 h incubation. The expression of CD4, CD25, and Foxp3 in Treg was analyzed by flow cytometry assay while TGFβ1 level was determined by Cytometric Bead Array (CBA).ResultsThis study showed that the percentage of CD4+CD25+Foxp3+ iTreg cells was significantly increased in T1 and T2. This finding was aligned with the significant increase of TGFβ1 level.ConclusionMSCs promote iTreg cells generation from human SLE PBMCs by releasing TGFβ1 to control SLE disease.Copyright © 2020 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.

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