STAT1 hyperphosphorylation and defective IL12R/IL23R signaling underlie defective immunity in autosomal dominant chronic mucocutaneous candidiasis.

We recently reported the genetic cause of autosomal dominant chronic mucocutaneous candidiasis (AD-CMC) as a mutation in the STAT1 gene. In the present study we show that STAT1 Arg274Trp mutations in the coiled-coil (CC) domain is the genetic cause of AD-CMC in three families of patients. Cloning an...

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Autores principales:	Sanne P Smeekens, Theo S Plantinga, Frank L van de Veerdonk, Bas Heinhuis, Alexander Hoischen, Leo A B Joosten, Peter D Arkwright, Andrew Gennery, Bart Jan Kullberg, Joris A Veltman, Desa Lilic, Jos W M van der Meer, Mihai G Netea
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b0055083eef94cb782b734cc171798d8
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spelling	oai:doaj.org-article:b0055083eef94cb782b734cc171798d82021-11-18T07:32:04ZSTAT1 hyperphosphorylation and defective IL12R/IL23R signaling underlie defective immunity in autosomal dominant chronic mucocutaneous candidiasis.1932-620310.1371/journal.pone.0029248https://doaj.org/article/b0055083eef94cb782b734cc171798d82011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22195034/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203We recently reported the genetic cause of autosomal dominant chronic mucocutaneous candidiasis (AD-CMC) as a mutation in the STAT1 gene. In the present study we show that STAT1 Arg274Trp mutations in the coiled-coil (CC) domain is the genetic cause of AD-CMC in three families of patients. Cloning and transfection experiments demonstrate that mutated STAT1 inhibits IL12R/IL-23R signaling, with hyperphosphorylation of STAT1 as the likely underlying molecular mechanism. Inhibition of signaling through the receptors for IL-12 and IL-23 leads to strongly diminished Th1/Th17 responses and hence to increased susceptibility to fungal infections. The challenge for the future is to translate this knowledge into novel strategies for the treatment of this severe immunodeficiency.Sanne P SmeekensTheo S PlantingaFrank L van de VeerdonkBas HeinhuisAlexander HoischenLeo A B JoostenPeter D ArkwrightAndrew GenneryBart Jan KullbergJoris A VeltmanDesa LilicJos W M van der MeerMihai G NeteaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 12, p e29248 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sanne P Smeekens Theo S Plantinga Frank L van de Veerdonk Bas Heinhuis Alexander Hoischen Leo A B Joosten Peter D Arkwright Andrew Gennery Bart Jan Kullberg Joris A Veltman Desa Lilic Jos W M van der Meer Mihai G Netea STAT1 hyperphosphorylation and defective IL12R/IL23R signaling underlie defective immunity in autosomal dominant chronic mucocutaneous candidiasis.
description	We recently reported the genetic cause of autosomal dominant chronic mucocutaneous candidiasis (AD-CMC) as a mutation in the STAT1 gene. In the present study we show that STAT1 Arg274Trp mutations in the coiled-coil (CC) domain is the genetic cause of AD-CMC in three families of patients. Cloning and transfection experiments demonstrate that mutated STAT1 inhibits IL12R/IL-23R signaling, with hyperphosphorylation of STAT1 as the likely underlying molecular mechanism. Inhibition of signaling through the receptors for IL-12 and IL-23 leads to strongly diminished Th1/Th17 responses and hence to increased susceptibility to fungal infections. The challenge for the future is to translate this knowledge into novel strategies for the treatment of this severe immunodeficiency.
format	article
author	Sanne P Smeekens Theo S Plantinga Frank L van de Veerdonk Bas Heinhuis Alexander Hoischen Leo A B Joosten Peter D Arkwright Andrew Gennery Bart Jan Kullberg Joris A Veltman Desa Lilic Jos W M van der Meer Mihai G Netea
author_facet	Sanne P Smeekens Theo S Plantinga Frank L van de Veerdonk Bas Heinhuis Alexander Hoischen Leo A B Joosten Peter D Arkwright Andrew Gennery Bart Jan Kullberg Joris A Veltman Desa Lilic Jos W M van der Meer Mihai G Netea
author_sort	Sanne P Smeekens
title	STAT1 hyperphosphorylation and defective IL12R/IL23R signaling underlie defective immunity in autosomal dominant chronic mucocutaneous candidiasis.
title_short	STAT1 hyperphosphorylation and defective IL12R/IL23R signaling underlie defective immunity in autosomal dominant chronic mucocutaneous candidiasis.
title_full	STAT1 hyperphosphorylation and defective IL12R/IL23R signaling underlie defective immunity in autosomal dominant chronic mucocutaneous candidiasis.
title_fullStr	STAT1 hyperphosphorylation and defective IL12R/IL23R signaling underlie defective immunity in autosomal dominant chronic mucocutaneous candidiasis.
title_full_unstemmed	STAT1 hyperphosphorylation and defective IL12R/IL23R signaling underlie defective immunity in autosomal dominant chronic mucocutaneous candidiasis.
title_sort	stat1 hyperphosphorylation and defective il12r/il23r signaling underlie defective immunity in autosomal dominant chronic mucocutaneous candidiasis.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/b0055083eef94cb782b734cc171798d8
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STAT1 hyperphosphorylation and defective IL12R/IL23R signaling underlie defective immunity in autosomal dominant chronic mucocutaneous candidiasis.

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