Rora regulates activated T helper cells during inflammation
Liora, V.; Walker, J. A.; Henriksson, J.; Miao, Z.; Natan, E.; Kar, G.; Clare, S.; Barlow, J. L.; Charidemou, E.; Mamanova, L.; Chen, X.; Proserpio, V.; Pramanik, J.; Woodhouse, S.; Protasio, A. V.; Efremova, M.; Berriman, M.; Dougan, G.; Fisher, J.; Marioni, J. C.; McKenzie, A. N.; Teichmann, S. A.
Show abstract
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, possibly through several downstream pathways, and is under control of the local microenvironment.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Cell-intrinsic IL4R alpha independence of large intestinal RELMα+ Ym1+ macrophages 96%
- Citrobacter rodentium infection activates colonic lamina propria group 2 innate lymphoid cells 95%
- Microbiota instruct IL-17A-producing innate lymphoid cells to promote skin inflammation in cutaneous leishmaniasis 94%
Similar papers in this journal
- Over-expression Screen of Interferon-Stimulated Genes Identifies RARRES3 as a Restrictor of Toxoplasma gondii Infection 95%
- An evolutionary recent IFN-IL-6-CEBP axis is linked to monocyte expansion and tuberculosis severity in humans 94%
- A genome-wide screen in macrophages identifies new regulators of IFNγ-inducible MHCII that contribute to T cell activation 94%
Similar papers in this journal
- Multiple environmental signaling pathways control the differentiation of RORγt-expressing regulatory T cells 95%
- Comprehensive sequencing of the lung neuroimmune landscape in response to asthmatic induction 95%
- Mmp17-deficient mice exhibit heightened goblet cell effector expression in the colon and increased resistance to chronic Trichuris muris infection 94%
Similar papers in this journal
- Deficiency in Bhlhe40 impairs resistance to H. polygyrus bakeri and reveals novel Csf2rb-dependent regulation of anti-helminth immunity 95%
- CNBP, REL, and BHLHE40 variants are associated with IL-12 and IL-10 responses and tuberculosis risk 95%
- CXCR6 promotes dermal CD8+ T cell survival and transition to long-term tissue residence 95%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.