ICOSL expression in human bone marrow-derived mesenchymal stem cells promotes induction of regulatory T cells

Autor: Myung-Shin Jeon, Si-Na Kim, TacGhee Yi, Sun U. Song, Hyun-Joo Lee
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
CD4-Positive T-Lymphocytes
Cellular differentiation
chemical and pharmacologic phenomena
Bone Marrow Cells
Lymphocyte proliferation
Lymphocyte Activation
Mesenchymal Stem Cell Transplantation
T-Lymphocytes
Regulatory
Article
Inducible T-Cell Co-Stimulator Protein
03 medical and health sciences
Inducible T-Cell Co-Stimulator Ligand
Phosphatidylinositol 3-Kinases
0302 clinical medicine
Downregulation and upregulation
Humans
IL-2 receptor
Cell Proliferation
Multidisciplinary
Chemistry
Mesenchymal stem cell
FOXP3
Gene Expression Regulation
Developmental
hemic and immune systems
Cell Differentiation
Mesenchymal Stem Cells
Coculture Techniques
Cell biology
Interleukin-10
Interleukin 10
030104 developmental biology
Signal transduction
Proto-Oncogene Proteins c-akt
030215 immunology
Signal Transduction
Zdroj: Scientific Reports
SCIENTIFIC REPORTS(7)
ISSN: 2045-2322
Popis: Mesenchymal stem cells (MSCs) can modulate lymphocyte proliferation and function. One of the immunomodulatory functions of MSCs involves CD4+CD25+FoxP3+ regulatory T cells (Tregs), which negatively regulate inflammatory responses. MSC-mediated Treg induction is supposed to be regulated by mechanisms requiring both soluble and cell contact-dependent factors. Although the involvement of soluble factors has been revealed, the contact-dependent mechanisms in MSC-mediated Treg induction remain unclear. We attempted to identify molecule(s) other than secreted factors that are responsible for MSC-mediated Treg induction and to uncover the underlying mechanisms. Under in vitro Treg-inducing conditions, ICOSL expression in MSCs coincided with Treg induction in co-cultures of MSCs with CD4+ T cells. When cultured in a transwell plate, MSCs failed to induce Tregs. Neutralization or knockdown of ICOSL significantly reduced Tregs and their IL-10 release. ICOSL overexpression in MSCs promoted induction of functional Tregs. ICOSL-ICOS signaling promoted Treg differentiation from CD4+ T cells through activation of the phosphoinositide 3-kinase-Akt pathway. MSCs primed with Interleukin-1β significantly induced Tregs through ICOSL upregulation. We demonstrated that the Treg-inducing activity of MSCs is proportionate to their basal ICOSL expression. This study provides evidence that ICOSL expression in human MSCs plays an important role in contact-dependent regulation of MSC-mediated Treg induction.
Databáze: OpenAIRE
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