Blimp-1 Functions as a Molecular Switch to Prevent Inflammatory Activity in Foxp3+RORγt+ Regulatory T Cells

Academic Article

Abstract

  • Foxp3+ regulatory T cells (Treg) are essential modulators of immune responses, but the molecular mechanisms underlying their function are not fully understood. Here we show that the transcription factor Blimp-1 is a crucial regulator of the Foxp3+RORγt+ Treg subset. The intrinsic expression of Blimp-1 in these cells is required to prevent production of Th17-associated cytokines. Direct binding of Blimp-1 to the Il17 locus in Treg is associated with inhibitory histone modifications but unaltered binding of RORγt. In the absence of Blimp-1, the Il17 locus is activated, with increased occupancy of the co-activator p300 and abundant binding of the transcriptional regulator IRF4, which is required, along with RORγt, for IL-17 expression in the absence of Blimp-1. We also show that despite their sustained expression of Foxp3, Blimp-1−/− RORγt+IL-17-producing Treg lose suppressor function and can promote intestinal inflammation, indicating that repression of Th17-associated cytokines by Blimp-1 is a crucial requirement for RORγt+ Treg function. Ogawa et al. demonstrate that the transcription factor Blimp-1 is required to prevent production of Th17-associated cytokines and inflammatory activity of microbiota-specific Foxp3+RORγt+ Treg. These findings uncover a critical role for Blimp-1 in Foxp3+ Treg function and shed light on the intricate mechanisms underlying Treg phenotypic stability.
  • Authors

    Published In

  • Cell Reports  Journal
  • Digital Object Identifier (doi)

    Author List

  • Ogawa C; Bankoti R; Nguyen T; Hassanzadeh-Kiabi N; Nadeau S; Porritt RA; Couse M; Fan X; Dhall D; Eberl G
  • Start Page

  • 19
  • End Page

  • 28.e5
  • Volume

  • 25
  • Issue

  • 1