NDLI: STAT1 Hyperphosphorylation and Defective IL12R/IL23R Signaling Underlie Defective Immunity in Autosomal Dominant Chronic Mucocutaneous Candidiasis

Content Provider	PubMed Central
Author	Smeekens, Sanne P. Plantinga, Theo S. Van, De Veerdonk Frank L. Bas, Heinhuis Alexander, Hoischen Joosten, Leo A. B. Arkwright, Peter D. Andrew, Gennery Kullberg, Bart Jan Veltman, Joris A. Lilic, Desa Meer, Jos W. M. Van Der Netea, Mihai G.
Editor	Georg, Häcker
Copyright Year	2011
Abstract	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.
Related Links	http://dx.doi.org/10.1371/journal.pone.0029248
Starting Page	29248
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	12
Volume Number	6
Language	English
Publisher	Public Library of Science
Publisher Date	2011-12-14
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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STAT1 Hyperphosphorylation and Defective IL12R/IL23R Signaling Underlie Defective Immunity in Autosomal Dominant Chronic Mucocutaneous Candidiasis