Blimp1 is required to repress Foxp3+ regulatory T cell pathogenic activity in mice. Mus musculus

Foxp3+Tregcells are essential modulators of immune responses but under specific conditions can acquire inflammatory properties and potentially contribute to disease pathogenesis. Here we show that the transcription factor Blimp1 is a critical regulator of Foxp3+Treg functional plasticity. The intrinsic expression of Blimp1 was required to prevent Treg from producing Th17-associated cytokines and acquiring an inflammatory phenotype while preserving Foxp3 expression. Mechanistically, Blimp1 acts as a direct repressor of the Il17a/Il17f genes in Foxp3+Treg and binding of Blimp1 at this locus is associated with altered chromatin status, reduced binding the co-activator p300, unaltered binding of the Th17-asssociated transcription factor RORt and more abundant binding of IRF4, which was required for the production of IL17A in Blimp1-deficient Foxp3+Tregcells, as shown by IRF4 siRNA-mediated knockdown. Consistent with their capacity to produce inflammatory cytokines, Blimp1-deficient Foxp3+Treg exacerbate Th17-mediated inflammation in vivo indicating that Blimp1 is required to prevent Treg cells from acquiring pathogenic properties Overall design: Total RNA from sorted Ctrl and Blimp1 CKO Foxp3 GFP+ pTreg cells