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

Cell Reports2018Vol. 25(1), pp. 19–28.e5

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Chihiro Ogawa, Rashmi Bankoti, Truc Nguyen, Nargess Hassanzadeh‐Kiabi, Samantha Nadeau, Rebecca A. Porritt, Michael Couse, Xuemo Fan, Deepti Dhall, Gérard Eberl, Caspar Ohnmacht, Gislâine A. Martins

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.

Citations Over TimeTop 10% of 2018 papers

Abstract

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