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© Research
Publication : Cell reports

Blimp-1 Functions as a Molecular Switch to Prevent Inflammatory Activity in Foxp3RORγt Regulatory T Cells

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Cell reports - 02 Oct 2018

Ogawa C, Bankoti R, Nguyen T, Hassanzadeh-Kiabi N, Nadeau S, Porritt RA, Couse M, Fan X, Dhall D, Eberl G, Ohnmacht C, Martins GA

Link to Pubmed [PMID] – 30282028

Cell Rep 2018 10;25(1):19-28.e5

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 Foxp3RORγt 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 RORγtIL-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.

https://www.ncbi.nlm.nih.gov/pubmed/30282028