| First Author | Ogawa C | Year | 2018 |
| Journal | Cell Rep | Volume | 25 |
| Issue | 1 | Pages | 19-28.e5 |
| PubMed ID | 30282028 | Mgi Jnum | J:270854 |
| Mgi Id | MGI:6278795 | Doi | 10.1016/j.celrep.2018.09.016 |
| Citation | Ogawa C, et al. (2018) Blimp-1 Functions as a Molecular Switch to Prevent Inflammatory Activity in Foxp3(+)RORgammat(+) Regulatory T Cells. Cell Rep 25(1):19-28.e5 |
| abstractText | 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(+)RORgammat(+) 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 RORgammat. 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 RORgammat, for IL-17 expression in the absence of Blimp-1. We also show that despite their sustained expression of Foxp3, Blimp-1(-/-) RORgammat(+)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 RORgammat(+) Treg function. |
