PLX178392

GSE112176: A Foxp3 mutation drives Th2 effector function in regulatory T cells

• Organsim mouse
• Type RNASEQ
• Target gene
• Project ARCHS4

Regulatory T (Treg) cells maintain immune tolerance through the action of the master regulator FOXP3, a transcription factor crucial for Treg cells function and homeostasis. We identified an IPEX patient with a FOXP3 mutation in the domain swap interface of the protein (mutant M370I). Recapitulation of this Foxp3 variant in mice led to an autoimmune syndrome similar to the patient and consistent with an unrestrained Th2 immune response. Genomic analysis of Treg cells by RNA-seq, Foxp3 ChIP-seq and H3K27ac-HiChIP revealed a specific de-repression of the T helper type 2 (Th2) transcriptional program leading to the generation of Th2-like Treg cells that are unable to suppress extrinsic Th2 cells. Th2-like Treg cells are characterized by increased intra-chromosomal interactions in the Th2 locus leading to type-2 cytokines production. Our research provides cellular and molecular characterizations of mechanisms used by Foxp3 to restrain Th2 transdifferentiation and promote optimal Treg suppressive function and stability. SOURCE: Frederic Van Gool (Frederic.VanGool@ucsf.edu) - UCSF