A novel human STAT3 mutation presents with autoimmunity involving Th17 hyperactivation

Oncotarget
Judith WienkeSytze de Roock

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.

References

Sep 20, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Timothy J HarrisCharles G Drake
Jul 22, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Danielle T AveryStuart G Tangye
May 18, 2013·Nature Reviews. Immunology·Stuart G TangyeElissa K Deenick
Oct 22, 2013·The Journal of Allergy and Clinical Immunology·Isaac J NijmanMarielle E van Gijn
Mar 7, 2014·Current Opinion in Immunology·Alisa KaneStuart G Tangye
Jul 21, 2014·Nature Genetics·Sarah E FlanaganAndrew T Hattersley

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Citations

Nov 7, 2019·Current Opinion in Pediatrics·Natalia S Chaimowitz, Lisa R Forbes
Apr 26, 2016·Journal of Immunology Research·Juan ShiXiaoming Liu
Nov 23, 2016·Clinical Reviews in Allergy & Immunology·Pandiarajan VigneshSurjit Singh
Feb 24, 2018·Frontiers in Immunology·Elissa K DeenickCindy S Ma
Oct 4, 2018·Expert Review of Clinical Immunology·Peter Olbrich, Alexandra F Freeman
Dec 5, 2019·Frontiers in Pediatrics·Shahrzad BakhtiarEleonora Gambineri
May 22, 2016·Autoimmunity·Mark Plander, Bernadette Kalman
Mar 3, 2019·The Journal of Allergy and Clinical Immunology. in Practice·Alexandre FabreLisa Giovannini-Chami
Aug 21, 2020·Molecular and Cellular Endocrinology·Mariana Gutiérrez
Jun 12, 2021·The Journal of Experimental Medicine·Jeremy T WarshauerMark S Anderson

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Methods Mentioned

BETA
flow cytometry

Related Concepts

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Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.

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