FoxP3 scanning mutagenesis reveals functional variegation and mild mutations with atypical autoimmune phenotypes.

ABSTRACT: FoxP3⁺ regulatory T cells (Tregs) are a central element of immunological tolerance. FoxP3 is the key determining transcription factor of the Treg lineage, interacting with numerous cofactors and transcriptional targets to determine the many facets of Treg function. Its absence leads to devastating lymphoproliferation and autoimmunity in scurfy mutant mice and immunodysregulation polyendocrinopathy enteropathy X-linked (IPEX) patients. To finely map transcriptionally active regions of the protein, with respect to disease-causing variation, we performed a systematic alanine-scan mutagenesis of FoxP3, assessing mutational impacts on DNA binding and transcriptional activation or repression. The mutations affected transcriptional activation and repression in a variegated manne

SUBMITTER: Kwon HK 

PROVIDER: S-EPMC5777076 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature