Immunology: Hippo Signalling Influences T Cell Fate

RESEARCH HIGHLIGHTS

Nature Reviews Rheumatology | Published online 25 May 2017; doi:10.1038/nrrheum.2017.82

IMMUNOLOGY Hippo signalling influences T cell fate

The Hippo signalling pathway is signalling pathway, the transcriptional acetyltransferase Tip60 (also known primarily known for its roles in tissue coactivator TAZ (also known as WW as KAT5), thus targeting FOXP3 for TAZ...is homeostasis, organ size regulation domain-containing transcription proteasomal degradation. and tumour suppression. However, regulator protein 1), is required for the When Hippo signalling is inacti- required emerging evidence implicates key differentiation of inflammatory TH17 vated, TAZ translocates to the nucleus, for the components of this pathway in cells, but inhibits the differentiation of where it binds to and activates TEAD differentiation T cell development and function. immunosuppressive Treg cells. family transcription factors, leading of ... T 17 New research published in Nature TAZ expression was substan- to transcription of genes related to cell H Immunology now reveals that Hippo tially enriched in T 17 cells, and proliferation. Geng et al. demonstrated cells, but H signalling is an important regulator expression of the gene encoding TAZ that Treg cell-polarizing conditions inhibits the of the reciprocal differentiation was higher in memory CD4+ T cells induced high levels of expression of the differentiation of T helper 17 (TH17) cells and isolated from patients with rheuma- transcription factor TEAD1, which regulatory T (T ) cells, two T cell toid arthritis, Sjögren syndrome or disrupted the interaction of TAZ with of ... T cells reg reg subsets with prominent roles in inflammatory bowel disease than RORγt, FOXP3 and Tip60 by binding autoimmunity. Geng et al. show that in cells from healthy individuals. TAZ with higher affinity, thereby

a downstream effector of the Hippo Conversely, TAZ deficiency pro- promoting Treg cell differentiation.

tected mice from TH17 cell-driven Notably, knockout of TAZ or autoimmune diseases (experimental overexpression of TEAD1 induced

autoimmune encephalomyelitis and Treg cell differentiation, whereas a T cell transfer model of colitis). expression of a transgene encoding Mechanistically, TAZ promoted TAZ or disruption of Hippo signal-

TH17 differentiation and function ling promoted TH17 cell differentia- by directly binding to and activating tion. Together, the findings highlight RORγt (considered to be the master the critical role of Hippo signalling

transcriptional regulator of TH17 in T cell homeostasis. cells) and blocking the activity of Sarah Onuora

FOXP3 (the Treg cell master regula- ORIGINAL ARTICLE Geng, J. et al. tor, which has an inhibitory effect The transcriptional coactivator TAZ regulates

on RORγt). TAZ also impaired Treg reciprocal differentiation of TH17 cells and Treg cell development by disrupting the cells. Nat. Immunol. http://dx.doi.org/10.1038/ ni.3748 (2017) acetylation of FOXP3 by the histone Macmillan Publishers Limited