Immunomodulatory effects of adipose-derived mesenchymal stem cells on the gene expression of major transcription factors of T cell subsets.
It has been proposed that the immunomodulatory properties of mesenchymal stem cells (MSCs) play a crucial role in establishing and leading T lymphocytes, especially Th cell subsets, toward different functional subsets. To determine the effect of the immunomodulatory and regulatory functions of adipose-derived MSCs (AD-MSCs) on C57BL/6 spleen-isolated mononuclear cells (Spleen-MNCs), the gene expression of well-known effector and regulatory Th cell-related transcription factors, i.e., t-bet, GATA-3, Ror-γt and Foxp3, and their related cytokines, i.e., IFN-γ for Th1 cells, IL-4 for Th2 cells, IL-17 for Th17 cells and IL-10 and TGF-β for regulatory T cells, was studied using a co-culture condition system. The proliferation index of Spleen-MNCs was analyzed using a cell proliferation assay kit that utilized the CFSE staining method. Our findings indicate that AD-MSCs greatly impact the up-regulation of immunomodulatory cytokines, such as TGF-β (p<0.001), and the down-regulation of inflammatory cytokines, such as IFN-γ (p<0.005), and transcription factors, such as t-bet (p<0.001). Considering the immunomodulatory effects of MSCs in the differentiation of Th cell subsets, understanding and harnessing this property of MSCs could be a powerful strategy in the treatment of inflammatory autoimmune diseases such as multiple sclerosis.
Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Adel
A
Mohammadzadeh
Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. Electronic address: Pourfa@modares.ac.ir.
Ali Akbar
AA
Pourfathollah
Department of Immunology, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran.
Somayeh
S
Shahrokhi
Department of Immunology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Stem Cell Biology, Stem Cell Technology Research Center, Tehran, Iran.
Seyed Mahmoud
SM
Hashemi
Department of Stem Cell Biology, Stem Cell Technology Research Center, Tehran, Iran.
Sadegh Lotf Alah
SL
Moradi
Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Masoud
M
Soleimani
D000273:Adipose Tissue / Q000276:immunology*; D000818:Animals; D002450:Cell Communication; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005786:Gene Expression Regulation; D056747:Immunomodulation; D018836:Inflammation Mediators / Q000378:metabolism; D008213:Lymphocyte Activation; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D016207:Cytokines; D018836:Inflammation Mediators; D014157:Transcription Factors
AD-MSCs; Autoimmunity; Cell subsets; Immunomodulation