JunB is essential for IL-23-dependent pathogenicity of Th17 cells

Nat Commun. 2017 May 30:8:15628. doi: 10.1038/ncomms15628.

Abstract

CD4+ T-helper cells producing interleukin-17 (IL-17), known as T-helper 17 (TH17) cells, comprise heterogeneous subsets that exhibit distinct pathogenicity. Although pathogenic and non-pathogenic TH17 subsets share a common RORγt-dependent TH17 transcriptional programme, transcriptional regulatory mechanisms specific to each of these subsets are mostly unknown. Here we show that the AP-1 transcription factor JunB is critical for TH17 pathogenicity. JunB, which is induced by IL-6, is essential for expression of RORγt and IL-23 receptor by facilitating DNA binding of BATF at the Rorc locus in IL-23-dependent pathogenic TH17 cells, but not in TGF-β1-dependent non-pathogenic TH17 cells. Junb-deficient T cells fail to induce TH17-mediated autoimmune encephalomyelitis and colitis. However, JunB deficiency does not affect the abundance of gut-resident non-pathogenic TH17 cells. The selective requirement of JunB for IL-23-dependent TH17 pathogenicity suggests that the JunB-dependent pathway may be a therapeutic target for autoimmune diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic-Leucine Zipper Transcription Factors / genetics
  • CD4-Positive T-Lymphocytes / cytology
  • Cell Differentiation / genetics
  • Colitis / genetics
  • Encephalomyelitis, Autoimmune, Experimental / genetics
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Female
  • Interleukin-17 / genetics*
  • Interleukin-23 / metabolism*
  • Leukocytes, Mononuclear / cytology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism
  • Signal Transduction
  • Th17 Cells / cytology*
  • Transcription Factors / genetics*
  • Virulence

Substances

  • Basic-Leucine Zipper Transcription Factors
  • Batf protein, mouse
  • Il17a protein, mouse
  • Interleukin-17
  • Interleukin-23
  • JunB protein, mouse
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Transcription Factors