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
Hao Cheng, Lingbiao Wang, Biaolong Yang, Dan Li, Xiaoxia Wang, Xinnan Liu, Na Tian, Qianru Huang, Ru Feng, Zhengting Wang, Rui Liang, Sheng‐Ming Dai, Ling Lv, Ji Wu, Yuan‐Sheng Zang, Bin Li
Abstract
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.