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Cutting Edge: Inhibition of Glycogen Synthase Kinase 3 Activity Induces the Generation and Enhanced Suppressive Function of Human IL-10+ FOXP3+-Induced Regulatory T Cells.


ABSTRACT: IL-10 is critical for Foxp3+ regulatory T cell (Tregs)-mediated immune suppression, but how to efficiently upregulate IL-10 production in Tregs remains unclear. In this article, we show that human IL-10+ FOXP3+-induced regulatory T cell (iTreg) generation can be dramatically promoted by inhibiting GSK3 activity. IL-10+ FOXP3+ iTregs induced by GSK3 inhibition exhibit classical features of immune-suppressive T cells. We further demonstrate that IL-10+ iTregs exhibit enhanced suppressive function in both IL-10-dependent and -independent manners. The enhanced suppressive function of IL-10+ Tregs is not due to a single factor such as IL-10, although IL-10 may mediate this enhanced suppressive function to some extent. Mechanistically, the increased transcriptional activity of IL-10 promoter and the enhanced expression of C-Maf and BLIMP1 coordinately facilitate IL-10 expression in human iTregs under GSK3 inhibition. Our study provides a new strategy to generate human immune-suppressive IL-10+ FOXP3+ Tregs for immunotherapies.

SUBMITTER: Cheng H 

PROVIDER: S-EPMC7477744 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Cutting Edge: Inhibition of Glycogen Synthase Kinase 3 Activity Induces the Generation and Enhanced Suppressive Function of Human IL-10<sup>+</sup> FOXP3<sup>+</sup>-Induced Regulatory T Cells.

Cheng Hao H   Wang Lingbiao L   Yang Biaolong B   Li Dan D   Wang Xiaoxia X   Liu Xinnan X   Tian Na N   Huang Qianru Q   Feng Ru R   Wang Zhengting Z   Liang Rui R   Dai Sheng-Ming SM   Lv Ling L   Wu Ji J   Zang Yuan-Sheng YS   Li Bin B  

Journal of immunology (Baltimore, Md. : 1950) 20200819 6


IL-10 is critical for Foxp3<sup>+</sup> regulatory T cell (Tregs)-mediated immune suppression, but how to efficiently upregulate IL-10 production in Tregs remains unclear. In this article, we show that human IL-10<sup>+</sup> FOXP3<sup>+</sup>-induced regulatory T cell (iTreg) generation can be dramatically promoted by inhibiting GSK3 activity. IL-10<sup>+</sup> FOXP3<sup>+</sup> iTregs induced by GSK3 inhibition exhibit classical features of immune-suppressive T cells. We further demonstrate th  ...[more]

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