A novel human STAT3 mutation presents with autoimmunity involving Th17 hyperactivation

Judith Wienke, Willemijn Janssen, Rianne Scholman, Hilde Spits, Marielle van Gijn, Marianne Boes, Joris van Montfrans, Nicolette Moes, Sytze de Roock

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

31 Citaten (Scopus)


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.

Originele taal-2Engels
Pagina's (van-tot)20037-20042
Aantal pagina's6
Nummer van het tijdschrift24
StatusGepubliceerd - 2015
Extern gepubliceerdJa


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