A reversible KO model reveals therapeutic potentials of defective Tregs

To characterize Brg1-reexpressed Tregs, we treated 3-wks-old rKO1 mice with the low dose of TAM and compared gene expression patterns in Brg1-deleted (GFP+) vs. Brg1-reexpressed (GFP- ) Treg subsets isolated 7 days after TAM. Brg1-deletion in the mosaic females and Brg1-reexpression in rKO1 mice on Day 7 after TAM treatment affected 618 and 1352 genes, respectively, with only 241 genes shared, suggesting divergent roles of Brg1 under the physiological vs. inflammatory conditions. These genes can be divided into two categories: the “naïve genes” that are predominantly expressed in naïve Tregs and “activation/effector function genes” preferentially expressed in activated/effector Tregs. Our data collectively suggest that Brg1 reexpression acted (partly) in conjunction with inflammatory cytokines to convert Brg1-deleted Tregs into hyperactivated Tregs endowed with potent suppressive activity mRNA profiles of 3-4 weeks old wild type (WT) and Nrl-/- mice were generated by deep sequencing, in triplicate, using HiSeq X Ten. BioProject: PRJNA547476