IRF8-dependent molecular complexes control the Th9 transcriptional program

Etienne Humblin1,2, Marion Thibaudin1,2, Fanny Chalmin2

  • 1Univ. Bourgogne Franche-Comté, F-21000, Dijon, France.

Nature Communications
|December 14, 2017
PubMed

Insights

Interferon regulatory factor 8 (IRF8) is crucial for Th9 cell differentiation and function. This study reveals IRF8

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Interferon regulatory factors (IRFs) are key regulators of immune responses.
  • IRF4's role in CD4+ T cells is well-studied, but IRF8's function remains less understood.

Purpose of the Study:

  • To investigate the role of IRF8 in Th9 cell differentiation and function.
  • To elucidate the molecular mechanisms by which IRF8 regulates Th9 cell development.

Main Methods:

  • In vitro differentiation of Th9 cells.
  • In vivo studies using mouse models.
  • Analysis of transcription factor complexes and gene expression (Il9, Il4).

Main Results:

  • IRF8 is essential for Th9 differentiation both in vitro and in vivo.
  • IRF8 forms a complex with IRF4, PU.1, and BATF to enhance Il9 transcription.
  • IRF8, in complex with ETV6, represses Il4 expression.
  • IRF8-dependent Th9 cells exhibit anti-tumour effects in melanoma models.

Conclusions:

  • IRF8 plays a critical role in promoting the Th9 cell program and suppressing Il4 expression.
  • IRF8 modulates Th9 cell differentiation through specific transcription factor complexes.
  • IRF8 represents a potential therapeutic target for enhancing Th9 responses in cancer therapy.

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