Dysregulated IFN-γ signals promote autoimmunity in STAT1 gain-of-function syndrome.

ABSTRACT: Heterozygous signal transducer and activator of transcription 1 (STAT1) gain-of-function (GOF) mutations promote a clinical syndrome of immune dysregulation characterized by recurrent infections and predisposition to humoral autoimmunity. To gain insights into immune characteristics of STAT1-driven inflammation, we performed deep immunophenotyping of pediatric patients with STAT1 GOF syndrome and age-matched controls. Affected individuals exhibited dysregulated CD4⁺ T cell and B cell activation, including expansion of T_H1-skewed CXCR3⁺ populations that correlated with serum autoantibody titers. To dissect underlying immune mechanisms, we generated Stat1 GOF transgenic mice (Stat1^GOF mice) and confirmed the development of spon

SUBMITTER: Largent AD 

PROVIDER: S-EPMC11645977 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature