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BATF-Interacting Proteins Dictate Specificity in Th Subset Activity.

Yongyao Fu1,2, Byunghee Koh1, Makoto Kuwahara3

  • 1Herman B Wells Center for Pediatric Research, Department of Pediatrics, School of Medicine, Indiana University, Indianapolis, IN 46202.

Journal of Immunology (Baltimore, Md. : 1950)
|August 28, 2019
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Summary
This summary is machine-generated.

The basic leucine zipper (bZIP) transcription factor BATF directs cytokine production in T helper cells. JunB, c-Jun, and Bach2 cooperate with BATF to specify IL-9 and IL-17 induction in distinct T helper subsets.

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Area of Science:

  • Immunology
  • Molecular Biology
  • Transcription Factor Function

Background:

  • The basic leucine zipper (bZIP) transcription factor BATF regulates gene transcription in various T helper (Th) cell subsets.
  • BATF controls lineage-specific cytokine production, such as IL-9 in Th9 cells and IL-17 in Th17 cells, but the mechanisms for this subset specificity are not fully understood.

Purpose of the Study:

  • To identify BATF binding partners that mediate subset-specific functions in T helper cells.
  • To elucidate the molecular mechanisms underlying BATF-dependent IL-9 and IL-17 induction in Th9 and Th17 cells.

Main Methods:

  • Primary mouse T cell culture was utilized to investigate transcription factor interactions.
  • Quantitative analysis of cytokine production (IL-9, IL-17) and gene expression was performed.
  • Co-transduction experiments were conducted to assess the synergistic effects of transcription factors.

Main Results:

  • JunB and c-Jun, but not JunD, were found to promote IL-9 production in Th9 cells.
  • Ectopic expression of BATF with JunB or c-Jun partially induced IL-9 in Th17 cells, suggesting Jun family member expression levels are a limiting factor.
  • Bach2 was identified as a positive regulator of IL-9 production in Th9 cells, binding directly to the Il9 gene.
  • Co-expression of Bach2 and BATF significantly induced IL-9 production in both Th9 and Th17 cells.

Conclusions:

  • JunB, c-Jun, and Bach2 cooperate with BATF to confer specificity to BATF-mediated cytokine induction in Th subsets.
  • These findings reveal a complex regulatory network involving BATF and its partners in determining T helper cell lineage-specific functions.