PT - JOURNAL ARTICLE AU - Liora Haim-Vilmovsky AU - Jennifer A Walker AU - Johan Henriksson AU - Zhichao Miao AU - Eviatar Natan AU - Gozde Kar AU - Simon Clare AU - Jillian L Barlow AU - Evelina Charidemou AU - Lira Mamanova AU - Xi Chen AU - Valentina Proserpio AU - Jhuma Pramanik AU - Steven Woodhouse AU - Anna V Protasio AU - Mirjana Efremova AU - Matt Berriman AU - Gordon Dougan AU - Jasmin Fisher AU - John C Marioni AU - Andrew NJ McKenzie AU - Sarah A Teichmann TI - <em>Rora</em> regulates activated T helper cells during inflammation AID - 10.1101/709998 DP - 2019 Jan 01 TA - bioRxiv PG - 709998 4099 - http://biorxiv.org/content/early/2019/08/08/709998.short 4100 - http://biorxiv.org/content/early/2019/08/08/709998.full AB - The transcription factor Rora has been shown to be important for the development of ILC2 and the regulation of ILC3, macrophages and Treg cells. Here we investigate the role of Rora across CD4+ T cells, both in vitro as well as in the context of several in vivo type 2 infection models. We dissect the function of Rora using overexpression and a CD4-conditional Rora-knockout mouse, as well as a RORA-reporter mouse. We establish the importance of Rora in CD4+ T cells for controlling lung inflammation induced by Nippostrongylus brasiliensis infection, and have measured the effect on downstream genes using RNA-seq. Using a systematic stimulation screen of CD4+ T cells, coupled with RNA-seq, we identify upstream regulators of Rora, most importantly IL-33 and CCL7. Our data suggest that Rora is a negative regulator of the immune system, involved in a range of pathways, under control of the local microenvironment.