Notch1 modulates mesenchymal stem cells mediated regulatory T-cell induction

被引：70

作者：

Del Papa, Beatrice ^{[1
]}

Sportoletti, Paolo ^{[1
]}

Cecchini, Debora ^{[1
]}

Rosati, Emanuela ^{[3
]}

Balucani, Chiara ^{[1
]}

Baldoni, Stefano ^{[1
]}

Fettucciari, Katia ^{[3
]}

Marconi, Pierfrancesco ^{[3
]}

Martelli, Massimo F. ^{[1
]}

Falzetti, Franca ^{[1
]}

Di Ianni, Mauro ^{[1
,2
]}

机构：

[1] Univ Perugia, Hematol & Clin Immunol Sect, Dept Clin & Expt Med, I-06100 Perugia, Italy

[2] Univ Aquila, Chair Hematol, Dept Internal Med & Publ Hlth, I-67100 Laquila, Italy

[3] Univ Perugia, Gen Pathol & Immunol Sect, Dept Clin & Expt Med, I-06100 Perugia, Italy

来源：

EUROPEAN JOURNAL OF IMMUNOLOGY | 2013年 / 43卷 / 01期

关键词：

Immune regulation; Mesenchymal stem cells; Notch1; Tolerance; Treg cells; TGF-BETA; GATA3; EXPRESSION; GENERATION; FOXP3; DIFFERENTIATION; OVEREXPRESSION; ANTIGEN; CD4(+); LIGAND;

D O I：

10.1002/eji.201242643

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

Notch1 signaling is involved in regulatory T (Treg)-cell differentiation. We previously demonstrated that, when cocultured with CD3+ cells, mesenchymal stem cells (MSCs) induced a T-cell population with a regulatory phenotype. Here, we investigated the molecular mechanism underlying MSC induction of human Treg cells. We show that the Notch1 pathway is activated in CD4+ T cells cocultured with MSCs. Inhibition of Notch1 signaling through GSI-I or the Notch1 neutralizing antibody reduced expression of HES1 (the Notch1 downstream target) and the percentage of MSC-induced CD4+CD25highFOXP3+ cells in vitro. Moreover, we demonstrate that FOXP3 is a downstream target of Notch signaling in human cells. No crosstalk between Notch1 and TGF-beta signaling pathways was observed in our experimental system. Together, these findings indicate that activation of the Notch1 pathway is a novel mechanism in the human Treg-cell induction mediated by MSCs.

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收藏

页码：182 / 187

页数：6

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