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A novel human STAT3 mutation presents with autoimmunity involving Th17 hyperactivation.

ABSTRACT: 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.

SUBMITTER: Wienke J

PROVIDER: S-EPMC4652985 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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A novel human STAT3 mutation presents with autoimmunity involving Th17 hyperactivation.

Wienke Judith J Janssen Willemijn W Scholman Rianne R Spits Hilde H van Gijn Marielle M Boes Marianne M van Montfrans Joris J Moes Nicolette N de Roock Sytze S

Oncotarget 20150801 24

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 t ...[more]

PMID: 26343524

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