The Th17 immune response is controlled by the Rel–RORγ–RORγT transcriptional axis
Copyright policy )The Th17 immune response is controlled by the Rel–RORγ–RORγT transcriptional axis
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.
- University of Pennsylvania United States
- Cornell University United States
- Moffitt Cancer Center United States
- University of Pennsylvania, Perelman school of medicine, / Radiology Dpt United States
- UNIVERSITY OF PENNSYLVANIA
Transcription, Genetic, Interleukin-17, Transcription Factor RelA, Cell Differentiation, Mice, Transgenic, Nuclear Receptor Subfamily 1, Group F, Member 1, Nuclear Receptor Subfamily 1, Group F, Member 3, Article, Proto-Oncogene Proteins c-rel, Mice, Inbred C57BL, Mice, Mice, Inbred NOD, Animals, Humans, Th17 Cells, Promoter Regions, Genetic, Signal Transduction
Transcription, Genetic, Interleukin-17, Transcription Factor RelA, Cell Differentiation, Mice, Transgenic, Nuclear Receptor Subfamily 1, Group F, Member 1, Nuclear Receptor Subfamily 1, Group F, Member 3, Article, Proto-Oncogene Proteins c-rel, Mice, Inbred C57BL, Mice, Mice, Inbred NOD, Animals, Humans, Th17 Cells, Promoter Regions, Genetic, Signal Transduction
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