Case Study: Mechanism for Increased Follicular Helper T Cell Development in Activated PI3K Delta Syndrome.

ABSTRACT: Gain-of-function variants in p110δ, the catalytic subunit of phosphatidylinositol 3-kinase (PI3K) expressed in lymphocytes, cause activated PI3-kinase δ syndrome (APDS), a primary immunodeficiency that is characterized by recurrent infections, viremia, lymphadenopathy, and autoimmunity. The mechanism of autoimmunity in APDS has not been well-understood. Here, we show the profound skewing of peripheral CD4⁺ T cells to a T follicular helper (T_FH) phenotype in a patient with APDS bearing a novel p110δ variant, Y524S. We also saw a diminishment of transient Foxp3 expression in activated T cells. Mechanistic studies revealed that both the new variant and a previously described, pathogenic variant (E81K) enhanced an interaction between intracellular Osteopontin and p85α. Th

SUBMITTER: Thauland TJ 

PROVIDER: S-EPMC6473200 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature