A novel human STAT3 mutation presents with autoimmunity involving Th17 hyperactivation

被引：37

作者：

Wienke, Judith ^{[1
]}

Janssen, Willemijn ^{[1
]}

Scholman, Rianne ^{[1
,2
]}

Spits, Hilde ^{[1
]}

van Gijn, Marielle ^{[3
]}

Boes, Marianne ^{[1
]}

van Montfrans, Joris ^{[1
]}

Moes, Nicolette ^{[4
]}

de Roock, Sytze ^{[1
]}

机构：

[1] Univ Med Ctr Utrecht, Lab Translat Immunol LTI, Paediat Immunol, Utrecht, Netherlands

[2] Univ Med Ctr Utrecht, Lab Translat Immunol LTI, Multiplex Core Facil, Utrecht, Netherlands

[3] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands

[4] Univ Groningen, Univ Med Ctr Groningen, Dept Paediat Gastroenterol Hepatol & Nutr, NL-9713 AV Groningen, Netherlands

来源：

ONCOTARGET | 2015年 / 6卷 / 24期

关键词：

autoimmunity; STAT3; Th17; IL-17; IL-21; DIFFERENTIATION; DISEASE; CELLS;

D O I：

10.18632/oncotarget.5042

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：20037 / 20042

页数：6

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