The transcriptional coactivator TAZ regulates reciprocal differentiation of T H 17 cells and T reg cells

An imbalance in the lineages of immunosuppressive regulatory T cells (T reg cells) and the inflammatory T H 17 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 T H 17 cell-inducing conditions and was required for T H 17 differentiation and T H 17 cell-mediated inflammatory diseases. TAZ was a critical co-activator of the T H 17-defining transcription factor ROR' 3t. In addition, TAZ attenuated T reg cell development by decreasing acetylation of the T reg cell master regulator Foxp3 mediated by the histone acetyltransferase Tip60, which targeted Foxp3 for proteasomal degradation. In contrast, under T reg cell-skewing conditions, TEAD1 expression and sequestration of TAZ from the transcription factors ROR' 3t and Foxp3 promoted T reg cell differentiation. Furthermore, deficiency in TAZ or overexpression of TEAD1 induced T reg cell differentiation, whereas expression of a transgene encoding TAZ or activation of TAZ directed T H 17 cell differentiation. Our results demonstrate a pivotal role for TAZ in regulating the differentiation of T reg cells and T H 17 cells.