A novel human STAT3 mutation presents with autoimmunity involving Th17 hyperactivation

Oncotarget. 2015 Aug 21;6(24):20037-42. doi: 10.18632/oncotarget.5042.


Mutations in STAT3 have recently been shown to cause autoimmune diseases through increased lymphoproliferation. We describe a novel Pro471Arg STAT3 mutation in a patient with multiple autoimmune diseases, causing hyperactivation of the Th17 pathway. We show that IL-17 production by primary T cells was enhanced and could not be further increased by IL-6, while IL-10 reduced Th17 cell numbers. Moreover, specific inhibition of STAT3 activation resulted in diminished IL-17 production. We show that the Pro471Arg STAT3 mutation yields both increased levels of IgA and IgG, probably due to high IL-21 levels. When remission was reached through medical intervention, IL-17 levels normalized and the clinical symptoms improved, supporting the idea that STAT3 gain-of-function mutations can cause hyperactivation of the Th17 pathway and thereby contribute to autoimmunity.

Keywords: IL-17; IL-21; Immune response; Immunity; Immunology and Microbiology Section; STAT3; Th17; autoimmunity.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Autoimmunity / immunology
  • Female
  • Humans
  • Mutation
  • STAT3 Transcription Factor / genetics*
  • STAT3 Transcription Factor / immunology*
  • Signal Transduction
  • Th17 Cells / immunology*


  • STAT3 Transcription Factor
  • STAT3 protein, human