TY - JOUR
T1 - Mapping Rora expression in resting and activated CD4+ T cells
AU - Haim-Vilmovsky, Liora
AU - Henriksson, Johan
AU - Walker, Jennifer A.
AU - Miao, Zhichao
AU - Natan, Eviatar
AU - Kar, Gozde
AU - Clare, Simon
AU - Barlow, Jillian L.
AU - Charidemou, Evelina
AU - Mamanova, Lira
AU - Chen, Xi
AU - Proserpio, Valentina
AU - Pramanik, Jhuma
AU - Woodhouse, Steven
AU - Protasio, Anna V.
AU - Efremova, Mirjana
AU - Griffin, Julian L.
AU - Berriman, Matt
AU - Dougan, Gordon
AU - Fisher, Jasmin
AU - Marioni, John C.
AU - McKenzie, Andrew N.J.
AU - Teichmann, Sarah A.
N1 - Publisher Copyright:
Copyright: © 2021 Haim-Vilmovsky et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2021/5
Y1 - 2021/5
N2 - 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 in general, but with an emphasis on Th2 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, possibly through several downstream pathways, and is under control of the local microenvironment.
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 in general, but with an emphasis on Th2 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, possibly through several downstream pathways, and is under control of the local microenvironment.
UR - https://www.scopus.com/pages/publications/85106170525
U2 - 10.1371/journal.pone.0251233
DO - 10.1371/journal.pone.0251233
M3 - Article
C2 - 34003838
AN - SCOPUS:85106170525
SN - 1932-6203
VL - 16
JO - PLoS ONE
JF - PLoS ONE
IS - 5 May
M1 - e0251233
ER -