The transcriptional coactivator TAZ regulates reciprocal differentiation of TH17 cells and Treg cells.
Jing GengShujuan YuHao ZhaoXiufeng SunXun LiPing WangXiaolin XiongLixin HongChangchuan XieJiahui GaoYiran ShiJiaqi PengRandy L JohnsonNengming XiaoLinrong LuJiahuai HanDawang ZhouLanfen ChenPublished in: Nature immunology (2017)
An imbalance in the lineages of immunosuppressive regulatory T cells (Treg cells) and the inflammatory TH17 subset of helper T cells leads to the development of autoimmune and/or inflammatory disease. Here we found that TAZ, a coactivator of TEAD transcription factors of Hippo signaling, was expressed under TH17 cell-inducing conditions and was required for TH17 differentiation and TH17 cell-mediated inflammatory diseases. TAZ was a critical co-activator of the TH17-defining transcription factor RORγt. In addition, TAZ attenuated Treg cell development by decreasing acetylation of the Treg cell master regulator Foxp3 mediated by the histone acetyltransferase Tip60, which targeted Foxp3 for proteasomal degradation. In contrast, under Treg cell-skewing conditions, TEAD1 expression and sequestration of TAZ from the transcription factors RORγt and Foxp3 promoted Treg cell differentiation. Furthermore, deficiency in TAZ or overexpression of TEAD1 induced Treg cell differentiation, whereas expression of a transgene encoding TAZ or activation of TAZ directed TH17 cell differentiation. Our results demonstrate a pivotal role for TAZ in regulating the differentiation of Treg cells and TH17 cells.
Keyphrases
- regulatory t cells
- transcription factor
- induced apoptosis
- cell cycle arrest
- single cell
- cell therapy
- oxidative stress
- endoplasmic reticulum stress
- poor prognosis
- cell proliferation
- signaling pathway
- stem cells
- cell death
- magnetic resonance
- endothelial cells
- immune response
- smoking cessation
- drug delivery
- dna methylation
- toll like receptor
- heat shock
- high glucose