title: The Th17 immune response is controlled by the Rel-RORγ-RORγ T transcriptional axis.
abstract: The Th17 cells use the retinoid-related orphan receptor-γ (Rorg or Rorc) to specify their differentiation and lineage-specific function. However, how Rorg is switched on during Th17 differentiation is unknown. We report here that c-Rel and RelA/p65 transcription factors drive Th17 differentiation by binding to and activating two distinct Rorg promoters that control RORγT and RORγ expression, respectively. Similar to RORγT, RORγ is selectively expressed in Th17 cells and is effective in specifying the Th17 phenotype. T cells deficient in c-Rel or RelA are significantly compromised in Th17 differentiation, and c-Rel-deficient mice are defective in Th17 responses. Thus, Th17 immunity is controlled by a Rel-RORγ-RORγT axis, and strategies targeting Rel/NF-κB can be effective for controlling Th17 cell-mediated diseases.
authors: Department of Pathology and Laboratory of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors: Qingguo
authors: Q
authors: Ruan
authors: Vasumathi
authors: V
authors: Kameswaran
authors: Yan
authors: Y
authors: Zhang
authors: Shijun
authors: S
authors: Zheng
authors: Jing
authors: J
authors: Sun
authors: Junmei
authors: J
authors: Wang
authors: Jennifer
authors: J
authors: DeVirgiliis
authors: Hsiou-Chi
authors: HC
authors: Liou
authors: Amer A
authors: AA
authors: Beg
authors: Youhai H
authors: YH
authors: Chen
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1 / Q000235:genetics / Q000276:immunology; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000276:immunology*; D011401:Promoter Regions, Genetic; D020569:Proto-Oncogene Proteins c-rel / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology* / Q000502:physiology; D051996:Transcription Factor RelA / Q000276:immunology; D014158:Transcription, Genetic
chemical_list: D020381:Interleukin-17; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D020569:Proto-Oncogene Proteins c-rel; D051996:Transcription Factor RelA