Tyrosine phosphatase SHP-2 mediates C-type lectin receptor-induced activation of the kinase Syk and anti-fungal TH17 responses

被引：102

作者：

Deng, Zihou ^{[1
]}

Ma, Shixin ^{[1
,2
]}

Zhou, Hao

Zang, Aiping ^{[1
]}

Fang, Yiyuan ^{[1
]}

Li, Tiantian ^{[1
]}

Shi, Huanjing ^{[1
]}

Liu, Mei ^{[1
]}

Du, Min ^{[1
]}

Taylor, Patricia R. ^{[3
]}

Zhu, Helen He ^{[4
]}

Chen, Jiangye ^{[5
]}

Meng, Guangxun ^{[1
]}

Li, Fubin ^{[6
,7
]}

Chen, Changbin ^{[1
]}

Zhang, Yan ^{[1
]}

Jia, Xin-Ming ^{[8
]}

Lin, Xin ^{[9
]}

Zhang, Xiaoming ^{[1
]}

Pearlman, Eric ^{[3
]}

Li, Xiaoxia ^{[2
]}

Feng, Gen-Sheng ^{[10
,11
]}

Xiao, Hui ^{[1
]}

机构：

[1] Chinese Acad Sci, Vaccine Ctr, Inst Pasteur Shanghai, Key Lab Mol Virol & Immunol, Shanghai, Peoples R China

[2] Cleveland Clin, Lerner Res Inst, Dept Immunol, Cleveland, OH 44106 USA

[3] Case Western Reserve Univ, Dept Ophthalmol & Visual Sci, Cleveland, OH 44106 USA

[4] Shanghai Jiao Tong Univ, Ren Ji Hosp, Sch Med, Renji Med X Clin Stem Cell Res Ctr,State Key Lab, Shanghai 200030, Peoples R China

[5] Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Biochem & Cell Biol, State Key Lab Mol Biol, Shanghai, Peoples R China

[6] Shanghai Jiao Tong Univ, Sch Med, Shanghai Inst Immunol, Shanghai 200030, Peoples R China

[7] Shanghai Jiao Tong Univ, Sch Med, Hongqiao Int Inst Med, Shanghai 200030, Peoples R China

[8] Tongji Univ, Sch Med, Dept Immunol, Shanghai 200092, Peoples R China

[9] Univ Texas MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA

[10] Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA

[11] Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA

来源：

NATURE IMMUNOLOGY | 2015年 / 16卷 / 06期

基金：

美国国家卫生研究院; 中国国家自然科学基金;

关键词：

PATTERN-RECOGNITION RECEPTOR; DENDRITIC CELLS; FUNGAL-INFECTIONS; CANDIDA-ALBICANS; IMMUNE-RESPONSES; INNATE IMMUNITY; HOST-DEFENSE; DECTIN-1; INDUCTION; PATHWAY;

D O I：

10.1038/ni.3155

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Fungal infection stimulates the canonical C-type lectin receptor (CLR) signaling pathway via activation of the tyrosine kinase Syk. Here we identify a crucial role for the tyrosine phosphatase SHP-2 in mediating CLR-induced activation of Syk. Ablation of the gene encoding SHP-2 (Ptpn11; called 'Shp-2' here) in dendritic cells (DCs) and macrophages impaired Syk-mediated signaling and abrogated the expression of genes encoding pro-inflammatory molecules following fungal stimulation. Mechanistically, SHP-2 operated as a scaffold, facilitating the recruitment of Syk to the CLR dectin-1 or the adaptor FcR gamma, through its N-SH2 domain and a previously unrecognized carboxy-terminal immunoreceptor tyrosine-based activation motif (ITAM). We found that DC-derived SHP-2 was crucial for the induction of interleukin 1 beta (IL-1 beta), IL-6 and IL-23 and anti-fungal responses of the T(H)17 subset of helper T cells in controlling infection with Candida albicans. Together our data reveal a mechanism by which SHP-2 mediates the activation of Syk in response to fungal infection.

引用

页码：642 / +

页数：13

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