The human Stat1 gain-of-function T385M mutation causes expansion of activated T-follicular helper/T-helper 1-like CD4 T cells and sex-biased autoimmunity in specific pathogen-free mice.

ABSTRACT:

Introduction

Humans with gain-of-function (GOF) mutations in STAT1 (Signal Transducer and Activator of Transcription 1), a potent immune regulator, experience frequent infections. About one-third, especially those with DNA-binding domain (DBD) mutations such as T385M, also develop autoimmunity, sometimes accompanied by increases in T-helper 1 (Th1) and T-follicular helper (Tfh) CD4 effector T cells, resembling those that differentiate following infection-induced STAT1 signaling. However, environmental and molecular mechanisms contributing to autoimmunity in STAT1 GOF patients are not defined.

Methods

We generated Stat1T385M/+ mutant mice to model the immune impacts of STAT1 DBD GOF under specific-pathogen free (SPF) conditions.

Results

Stat1T385M/+ lymphocytes had mor

SUBMITTER: Scott O 

PROVIDER: S-EPMC10235531 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature