STAT1 hyperphosphorylation and defective IL12R/IL23R signaling underlie defective immunity in autosomal dominant chronic mucocutaneous candidiasis.
STAT1 hyperphosphorylation and defective IL12R/IL23R signaling underlie defective immunity in autosomal dominant chronic mucocutaneous candidiasis.
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DOI：
10.1371/journal.pone.0029248
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Netea MG
中科院分区：
文献类型：
--
作者：
Smeekens SP;Plantinga TS;van de Veerdonk FL;Heinhuis B;Hoischen A;Joosten LA;Arkwright PD;Gennery A;Kullberg BJ;Veltman JA;Lilic D;van der Meer JW;Netea MG
我们最近报道了常染色体显性遗传慢性皮肤粘膜念珠菌病（AD-CMC）的遗传原因是STAT 1基因突变。在本研究中，我们表明，STAT 1 Arg 274 Trp突变的卷曲螺旋（CC）域是遗传原因的AD-CMC在三个家庭的患者。克隆和转染实验表明，突变的STAT 1抑制IL 12 R/IL-23 R信号转导，STAT 1的过度磷酸化可能是潜在的分子机制。通过IL-12和IL-23受体的信号传导的抑制导致Th 1/Th 17应答的强烈减弱，并因此导致对真菌感染的易感性增加。未来的挑战是将这些知识转化为治疗这种严重免疫缺陷的新策略。
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.
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影响因子：
30.8
作者：
Dupuis, S;Jouanguy, E;Casanova, JL
通讯作者：
Casanova, JL
影响因子：
4.4
作者：
Kao, CY;Chen, Y;Wu, R
通讯作者：
Wu, R
影响因子：
4.4
作者：
Chapgier, Ariane;Wynn, Robert F.;Arkwright, Peter D.
通讯作者：
Arkwright, Peter D.
DOI：
10.1084/jem.20110958
发表时间：
2011-08-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Liu L;Okada S;Kong XF;Kreins AY;Cypowyj S;Abhyankar A;Toubiana J;Itan Y;Audry M;Nitschke P;Masson C;Toth B;Flatot J;Migaud M;Chrabieh M;Kochetkov T;Bolze A;Borghesi A;Toulon A;Hiller J;Eyerich S;Eyerich K;Gulácsy V;Chernyshova L;Chernyshov V;Bondarenko A;Grimaldo RM;Blancas-Galicia L;Beas IM;Roesler J;Magdorf K;Engelhard D;Thumerelle C;Burgel PR;Hoernes M;Drexel B;Seger R;Kusuma T;Jansson AF;Sawalle-Belohradsky J;Belohradsky B;Jouanguy E;Bustamante J;Bué M;Karin N;Wildbaum G;Bodemer C;Lortholary O;Fischer A;Blanche S;Al-Muhsen S;Reichenbach J;Kobayashi M;Rosales FE;Lozano CT;Kilic SS;Oleastro M;Etzioni A;Traidl-Hoffmann C;Renner ED;Abel L;Picard C;Maródi L;Boisson-Dupuis S;Puel A;Casanova JL
通讯作者：
Casanova JL
DOI：
10.1084/jem.20091669
发表时间：
2010-02-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kisand K;Bøe Wolff AS;Podkrajsek KT;Tserel L;Link M;Kisand KV;Ersvaer E;Perheentupa J;Erichsen MM;Bratanic N;Meloni A;Cetani F;Perniola R;Ergun-Longmire B;Maclaren N;Krohn KJ;Pura M;Schalke B;Ströbel P;Leite MI;Battelino T;Husebye ES;Peterson P;Willcox N;Meager A
通讯作者：
Meager A