Format

Send to

Choose Destination
J Immunol. 2019 Aug 26. pii: ji1900128. doi: 10.4049/jimmunol.1900128. [Epub ahead of print]

BATF-Interacting Proteins Dictate Specificity in Th Subset Activity.

Author information

1
Herman B Wells Center for Pediatric Research, Department of Pediatrics, School of Medicine, Indiana University, Indianapolis, IN 46202.
2
Department of Microbiology and Immunology, School of Medicine, Indiana University, Indianapolis, IN 46202.
3
Department of Immunology, Ehime University, Shitsukawa, Toon-Shi, Ehime 791-0295, Japan; and.
4
Department of Biochemistry and Molecular Biology, School of Medicine, Indiana University, Indianapolis, IN 46202.
5
Herman B Wells Center for Pediatric Research, Department of Pediatrics, School of Medicine, Indiana University, Indianapolis, IN 46202; mkaplan2@iu.edu.

Abstract

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.

PMID:
31451674
DOI:
10.4049/jimmunol.1900128

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center