Gain-of-Function Mutation of Card14 Leads to Spontaneous Psoriasis-like Skin Inflammation through Enhanced Keratinocyte Response to IL-17A

被引：123

作者：

Wang, Mingchao ^{[1
]}

Zhang, Shanshan ^{[1
]}

Zheng, Guoxing ^{[1
]}

Huang, Junjiu ^{[2
]}

Zhou Songyang ^{[2
]}

Zhao, Xueqiang ^{[1
]}

Xin Lin ^{[1
]}

机构：

[1] Tsinghua Univ, Sch Med, Inst Immunol, Tsinghua Univ Peking Univ Jointed Ctr Life Sci, Beijing 100084, Peoples R China

[2] Sun Yat Sen Univ, Inst Hlth Aging Res, Sch Life Sci, Guangzhou 510275, Guangdong, Peoples R China

来源：

IMMUNITY | 2018年 / 49卷 / 01期

基金：

中国国家自然科学基金;

关键词：

KAPPA-B ACTIVATION; INNATE IMMUNITY; MECHANISMS; DISEASE; MICE; AXIS; GENETICS; MODERATE; CARMA1; TARGET;

D O I：

10.1016/j.immuni.2018.05.012

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Genetic mutations of CARD14 (encoding CARMA2) are observed in psoriasis patients. Here we showed that Card14(E138A/+) and Card14(Delta Q136/+) mice developed spontaneous psoriasis-like skin inflammation, which resulted from constitutively activated CARMA2 via self-aggregation leading to the enhanced activation of the IL-23-IL-17A cytokine axis. Card14(-/-) mice displayed attenuated skin inflammation in the imiquimod-induced psoriasis model due to impaired IL-17A signaling in keratinocytes. CARMA2, mainly expressed in keratinocytes, associates with the ACT1-TRAF6 signaling complex and mediates IL-17A-induced NF-kappa B and MAPK signaling pathway activation, which leads to expression of pro-inflammatory factors. Thus, CARMA2 serves as a key mediator of IL-17A signaling and its constitutive activation in keratinocytes leads to the onset of psoriasis, which indicates an important role of NF-kappa B activation in keratinocytes in psoriatic initiation.

引用

页码：66 / +

页数：19

共 38 条

[1] The paracaspase MALT1 mediates CARD14-induced signaling in keratinocytes [J].