A human STAT3 gain-of-function variant confers T cell dysregulation without predominant Treg dysfunction in mice.

ABSTRACT: Primary immune regulatory disorders (PIRD) represent a group of disorders characterized by immune dysregulation, presenting with a wide range of clinical disease, including autoimmunity, autoinflammation, or lymphoproliferation. Autosomal dominant germline gain-of-function (GOF) variants in STAT3 result in a PIRD with a broad clinical spectrum. Studies in patients have documented a decreased frequency of FOXP3+ Tregs and an increased frequency of Th17 cells in some patients with active disease. However, the mechanisms of disease pathogenesis in STAT3 GOF syndrome remain largely unknown, and treatment is challenging. We developed a knock-in mouse model harboring a de novo pathogenic human STAT3 variant (p.G421R) and found these mice developed T cell dysregulation, lymphoproliferation, and C

SUBMITTER: Schmitt EG 

PROVIDER: S-EPMC9675480 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature