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01-05-2015

Glycogen synthase kinase 3β inhibition promotes human iTreg differentiation and suppressive function

Authors: Yongxiang Xia, Han Zhuo, Yunjie Lu, Lei Deng, Runqiu Jiang, Long Zhang, Qin Zhu, Liyong Pu, Xuehao Wang, Ling Lu

Published in: Immunologic Research | Issue 1/2015

Abstract

Induced regulatory T cells (iTregs) are essential to maintain immunological tolerance, immune homeostasis and prevention of autoimmunity. Some studies suggest that glycogen synthase kinase 3β (GSK3β) is involved in the mouse iTreg differentiation; however, whether GSK3β inhibits or enhances iTreg differentiation is still a matter of controversy. To address this issue, we have utilized human naïve CD4⁺ T cells and investigated whether GSK3 activity changes during iTreg differentiation and whether altering GSK3 activity influences the development of iTregs and its suppressive function. As a constitutively activated kinase, during iTreg differentiation GSK3β became quickly deactivated (phosphorylated at serine 9), which is dependent on MAPK pathway rather than PI3-kinase/Akt pathway. Our results indicated that inhibition of GSK3β by specific inhibitors, SB216763 or TDZD-8, promoted the differentiation of iTreg and increased their suppressive activity. In contrast, overexpression of GSK3β significantly inhibited iTreg differentiation. Furthermore, GSK3β inhibition enhanced iTreg differentiation through the TGF-β/Smad3 pathway. Taken together, this study demonstrates that inhibition of GSK3β enhances human iTreg differentiation and its suppressive activity, and provides a rationale to target GSK3β as a novel immunotherapeutic strategy.

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Title: Glycogen synthase kinase 3β inhibition promotes human iTreg differentiation and suppressive function
Authors: Yongxiang Xia
Han Zhuo
Yunjie Lu
Lei Deng
Runqiu Jiang
Long Zhang
Qin Zhu
Liyong Pu
Xuehao Wang
Ling Lu
Publication date: 01-05-2015
Publisher: Springer US
Published in: Immunologic Research / Issue 1/2015
Print ISSN: 0257-277X
Electronic ISSN: 1559-0755
DOI: https://doi.org/10.1007/s12026-015-8635-3

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Glycogen synthase kinase 3β inhibition promotes human iTreg differentiation and suppressive function

Abstract

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