GSE98242
The AP-1 Transcription Factor JunB Is Required for Th17 Cell Differentiation
Interleukin (IL)-17-producing T helper (Th17) cells are crucial for host defense against extracellular microbes and pathogenesis of autoimmune diseases.  Here we show that the AP-1 transcription factor JunB is required for Th17 cell development.  Junb-deficient CD4+ T cells are able to develop in vitro into various helper T subsets except Th17.  The RNA-seq transcriptome analysis reveals that JunB is crucial for the Th17-specific gene expression program.  Junb-deficient mice are completely resistant to experimental autoimmune encephalomyelitis, a Th17-mediated inflammatory disease, and naive T helper cells from such mice fail to differentiate into Th17 cells.  JunB appears to activate Th17 signature genes by forming a heterodimer with BATF, another AP-1 factor essential for Th17 differentiation.  The mechanism whereby JunB controls Th17 cell development likely involves activation of the genes for the Th17 lineage-specifying orphan receptors ROR?t and ROR? and reduced expression of Foxp3, a transcription factor known to antagonize ROR?t function. Overall design: Naïve T cell, Th0 and Th17 mRNA profiles of wild type (WT) and Junb-/- mice were generated by deep sequencing, using Illumina HiSeq2500