MSCs-released TGFβ1 generate CD4+CD25+Foxp3+ in T-reg cells of human SLE PBMC
Darlan D.M., Munir D., Jusuf N.K., Putra A.
Abstract
Background/Purpose: Regulatory 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<sup>+</sup>, CD25<sup>+</sup>, and Foxp3<sup>+</sup> expression in iTreg cells from human SLE peripheral blood mononuclear cells (PBMCs). Methods: This 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). Results: This study showed that the percentage of CD4<sup>+</sup>CD25<sup>+</sup>Foxp3<sup>+</sup> iTreg cells was significantly increased in T1 and T2. This finding was aligned with the significant increase of TGFβ1 level. Conclusion: MSCs promote iTreg cells generation from human SLE PBMCs by releasing TGFβ1 to control SLE disease.
Protein phosphatase 2A reactivates FOXO3a through a dynamic interplay with 14-3-3 and AKT
Bucur O., Gao D., Hahn W.C., Hahn W.C., Hahn W.C., Khosravi-Far R., Rabinovitz I., Santos M.T., Singh A., Wei W., Ye M., Zhu S.
AMBRA1 Controls Regulatory T-Cell Differentiation and Homeostasis Upstream of the FOXO3-FOXP3 Axis
Battistini L., Becher J., Bonaldo P., Borsellino G., Botti G., Braghetta P., Campello S., Campello S., Caruana I., Cecconi F., Cecconi F., Cecconi F., Centonze D., Centonze D., Chrisam M., Cianfanelli V., Ciccosanti F., D'Acunzo P., D'Amelio M., D'Amelio M., De Bardi M., Fimia G.M., Fimia G.M., Furlan R., Gigantino V., La Rocca C., Locatelli F., Locatelli F., Mandolesi G., Martino G., Matarese G., Matarese G., Nazio F., Procaccini C., Procaccini C., Ruffini F., Simula L., Strappazzon F., Strappazzon F., Volpe E., Weber G.
PI3K signalling in B- and T-lymphocytes: New developments and therapeutic advances
Fruman D.A., Fruman D.A., So L., So L.
T Cell Receptor-Regulated TGF-β Type I Receptor Expression Determines T Cell Quiescence and Activation
Alegre M.-L., Chen W., Chen W., Chia C.P.Z., Jin W., Park S.A., Sun L., Tu E., Wang D., Zhang D., Zhang Y.E.
TGF-β1 maintains suppressor function and Foxp3 expression in CD4 +CD25+ regulatory T cells
Gavin M., Letterio J.J., Marie J.C., Rudensky A.Y., Gavin M., Letterio J.J., Marie J.C., Rudensky A.Y.
Mesenchymal stem cells inhibit human Th17 cell differentiation and function and induce a T regulatory cell phenotype
Ghannam S., Jorgensen C., Pene J., Torcy-Moquet G., Yssel H., Ghannam S., Jorgensen C., Pene J., Torcy-Moquet G., Yssel H.
Conversion of Peripheral CD4+CD25- Naive T Cells to CD4+CD25+ Regulatory T Cells by TGF-β Induction of Transcription Factor Foxp3
Chen W., Hardegen N., Jin W., Lei K.-J., Li L., Marinos N., McGrady G., Wahl S.M.
Foxp3 programs the development and function of CD4+CD25+ regulatory T cells
Fontenot J.D., Gavin M.A., Rudensky A.Y.
Cell contact, prostaglandin E2 and transforming growth factor beta 1 play non-redundant roles in human mesenchymal stem cell induction of CD4+CD25Highforkhead box P3+ regulatory T cells
Barry F.P., English K., Mahon B.P., Mahon B.P., Murphy M.J., Ryan J.M., Tobin L., Barry F.P., English K., Mahon B.P., Mahon B.P., Murphy M.J., Ryan J.M., Tobin L., Barry F.P., English K., Mahon B.P., Mahon B.P., Murphy M.J., Ryan J.M., Tobin L., Barry F.P., English K., Mahon B.P., Mahon B.P., Murphy M.J., Ryan J.M., Tobin L., Barry F.P., English K., Mahon B.P., Mahon B.P., Murphy M.J., Ryan J.M., Tobin L., Barry F.P., English K., Mahon B.P., Mahon B.P., Murphy M.J., Ryan J.M., Tobin L.
Reduced number and function of CD4+ CD25 high foxP3 + regulatory T cells in patients with systemic lupus erythematosus
Bykovskaia S.N., Lyssuk E.Y., Nassonov E.L., Soloviev S.K., Torgashina A.V.
Haider K.H., Ahmed Z.T., Ahmed O.T., Alkahlot R.H., Dairi A.W., Jowf G.I.A.
Handbook of Regenerative Medicine Cell Free Therapy Approach
Mao F., Wu Y., Ocansey D.K.W., Wang B., Song D., He C.
Autoimmunity Reviews
Darlan D.M., Lubis R.R., Munir D., Putra A., Alif I.
Open Access Macedonian Journal of Medical Sciences
Kamm J.L., McIlwraith C.W., Parlane N., Gee E.K., Riley C.B.
Frontiers in Veterinary Science
Chen Q., Wu M., Luo M., Yang C., You M., Chen Y.
Stem Cell Research and Therapy
Mao F., Yuan J., Ocansey D.K.W., Wei Z., Xu Z., Wang G.
Stem Cells International
Ramasamy R., Nasihun T., Putra A., Kustiyah A.R.
Open Access Macedonian Journal of Medical Sciences
Mao F., Yuan J., Xu X., Ocansey D.K.W., Cai X., Wei Z.
Stem Cells International
Yan S., Xu D., Wang J., Yang J., Sun J., Zhang J., Yang C., Tian Y., Zhang L., Li H.
Frontiers in Immunology
Liao Y., Liu M., Zeng G., Liang X., Li D., Wu S., Hu J., Ouyang Q., Xu S., Fu Z., Liao G., Tang Z., Cheng D.
Frontiers in Cell and Developmental Biology
