BATF-Interacting Proteins Dictate Specificity in Th Subset Activity

J Immunol. 2019 Oct 1;203(7):1989-1998. doi: 10.4049/jimmunol.1900128. Epub 2019 Aug 26.


The basic leucine zipper (bZIP) transcription factor BATF is expressed in multiple Th subsets and cooperates with other factors to regulate gene transcription. BATF activates lineage-specific cytokines in Th subsets, activating IL-9 in Th9 cells and IL-17 in Th17 cells, but not IL-9 or IL-17 in the reciprocal subset. The mechanism for this restricted activity is unclear. In this report, we define BATF binding partners that contribute to Th subset-specific functions. Although BATF and IRF4 are expressed in greater amounts in Th9 than Th17, increased expression of both factors is not sufficient to induce IL-9 in Th17 cells. BATF also requires heterodimer formation with Jun family members to bind DNA and induce gene expression. Using primary mouse T cell culture, we observed that JunB and c-Jun, but not JunD, promote IL-9 production in Th9 cells. Ectopic expression of BATF with either JunB or c-Jun generates modest, but significant, increases in IL-9 production in Th17 cells, suggesting that the low expression of Jun family members is one factor limiting the ability of BATF to induce IL-9 in Th17 cells. We further identified that Bach2 positively regulates IL-9 production by directly binding to the Il9 gene and by increasing transcription factor expression in Th9 cells. Strikingly, cotransduction of Bach2 and BATF significantly induces IL-9 production in both Th9 and Th17 cells. Taken together, our results reveal that JunB, c-Jun, and Bach2 cooperate with BATF to contribute to the specificity of BATF-dependent cytokine induction in Th subsets.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic-Leucine Zipper Transcription Factors / genetics
  • Basic-Leucine Zipper Transcription Factors / immunology*
  • Gene Expression Regulation / immunology*
  • Humans
  • Interferon Regulatory Factors / genetics
  • Interferon Regulatory Factors / immunology
  • Interleukin-9 / genetics
  • Interleukin-9 / immunology
  • Mice
  • Mice, Transgenic
  • Th17 Cells / cytology
  • Th17 Cells / immunology*
  • Transcription Factors / genetics
  • Transcription Factors / immunology


  • BACH2 protein, human
  • BATF protein, human
  • Bach2 protein, mouse
  • Basic-Leucine Zipper Transcription Factors
  • Batf protein, mouse
  • IL9 protein, human
  • Interferon Regulatory Factors
  • Interleukin-9
  • JunB protein, human
  • JunB protein, mouse
  • Transcription Factors
  • interferon regulatory factor-4