Single-cell analysis of FOXP3 deficiencies in humans and mice unmasks intrinsic and extrinsic CD4⁺ T cell perturbations.

ABSTRACT: FOXP3 deficiency in mice and in patients with immune dysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome results in fatal autoimmunity by altering regulatory T (T_reg) cells. CD4⁺ T cells in patients with IPEX syndrome and Foxp3-deficient mice were analyzed by single-cell cytometry and RNA-sequencing, revealing heterogeneous T_reg-like cells, some very similar to normal T_reg cells, others more distant. Conventional T cells showed no widespread activation or helper T cell bias, but a monomorphic disease signature affected all CD4⁺ T cells. This signature proved to be cell extrinsic since it was extinguished in mixed bone marrow chimeric mice and heterozygous mothers of patients with IPEX syndrome. Normal T_reg

SUBMITTER: Zemmour D 

PROVIDER: S-EPMC8173714 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature