The transcriptional coactivator TAZ regulates reciprocal differentiation of T17 cells and T cells.

An imbalance in the lineages of immunosuppressive regulatory T cells (T cells) and the inflammatory T17 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 T17 cell-inducing conditions and was required for T17 differentiation and T17 cell-mediated inflammatory diseases. TAZ was a critical co-activator of the T17-defining transcription factor RORγt. In addition, TAZ attenuated T cell development by decreasing acetylation of the T cell master regulator Foxp3 mediated by the histone acetyltransferase Tip60, which targeted Foxp3 for proteasomal degradation. In contrast, under T cell-skewing conditions, TEAD1 expression and sequestration of TAZ from the transcription factors RORγt and Foxp3 promoted T cell differentiation. Furthermore, deficiency in TAZ or overexpression of TEAD1 induced T cell differentiation, whereas expression of a transgene encoding TAZ or activation of TAZ directed T17 cell differentiation. Our results demonstrate a pivotal role for TAZ in regulating the differentiation of T cells and T17 cells.