Hyperactive PI3Kδ predisposes naive T cells to activation via aerobic glycolysis programs.

ABSTRACT: Activated phosphoinositide 3-kinase δ syndrome (APDS) is an autosomal-dominant combined immunodeficiency disorder resulting from pathogenic gain-of-function (GOF) mutations in the PIK3CD gene. Patients with APDS display abnormal T cell homeostasis. However, the mechanisms by which PIK3CD GOF contributes to this feature remain unknown. Here, with a cohort of children with PIK3CD GOF mutations from multiple regions of China and a corresponding CRISPR/Cas9 gene-edited mouse model, we reported that hyperactive PI3Kδ disrupted T_Naive cell homeostasis in the periphery by intrinsically promoting the growth, proliferation, and activation of T_Naive cells. Our results showed that PIK3CD GOF resulted in loss of the quiescence-associated gene expression profile in naive T cells a

SUBMITTER: Jia Y 

PROVIDER: S-EPMC8245563 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature