The Immune Adaptor ADAP Regulates Reciprocal TGF-beta 1-Integrin Crosstalk to Protect from Influenza Virus Infection

	The Immune Adaptor ADAP Regulates Reciprocal TGF-beta 1-Integrin Crosstalk to Protect from Influenza Virus Infection
	Li, CY; Jiao, SZ; Wang, GJ; Gao, YZ; Liu, C; He, XJ; Zhang, C; Xiao, J; Li, WY; Zhang, GQ
刊名	PLOS PATHOGENS
	2015
卷号	11 期号:4 页码:e1004824-e1004824
通讯作者	Li, CY (reprint author), Chinese Acad Sci, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, Innovat Ctr Cell Signaling Network,Key Lab Syst B, Shanghai, Peoples R China.,chenhualan@caas.cn ; hongyanwang@sibcb.ac.cn
英文摘要	Highly pathogenic avian influenza virus (HPAI, such as H5N1) infection causes severe cytokine storm and fatal respiratory immunopathogenesis in human and animal. Although TGF-beta 1 and the integrin CD103 in CD8(+) T cells play protective roles in H5N1 virus infection, it is not fully understood which key signaling proteins control the TGF-beta 1-integrin crosstalk in CD8(+) T cells to protect from H5N1 virus infection. This study showed that ADAP (Adhesion and Degranulation-promoting Adapter Protein) formed a complex with TRAF6 and TAK1 in CD8(+) T cells, and activated SMAD3 to increase autocrine TGF-beta 1 production. Further, TGF-beta 1 induced CD103 expression via an ADAP-, TRAF6- and SMAD3-dependent manner. In response to influenza virus infection (i.e. H5N1 or H1N1), lung infiltrating ADAP(-/-)CD8(+) T cells significantly reduced the expression levels of TGF-beta 1, CD103 and VLA-1. ADAP(-/-) mice as well as Rag1(-/-) mice receiving ADAP(-/-) T cells enhanced mortality with significant higher levels of inflammatory cytokines and chemokines in lungs. Together, we have demonstrated that ADAP regulates the positive feedback loop of TGF-beta 1 production and TGF-beta 1-induced CD103 expression in CD8(+) T cells via the T beta RI-TRAF6-TAK1-SMAD3 pathway and protects from influenza virus infection. It is critical to further explore whether the SNP polymorphisms located in human ADAP gene are associated with disease susceptibility in response to influenza virus infection.
学科主题	Microbiology; Parasitology; Virology
类目[WOS]	Microbiology ; Parasitology ; Virology
关键词[WOS]	GROWTH-FACTOR-BETA ; CD8(+) T-CELLS ; TRANSFORMING GROWTH-FACTOR-BETA-1 ; ACTIVATION ; EXPRESSION ; SMAD ; MICE ; PATHWAYS ; BINDING ; GENE
收录类别	SCI
语种	英语
WOS记录号	WOS:000354978000036
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/46]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Li, CY,Jiao, SZ,Wang, GJ,et al. The Immune Adaptor ADAP Regulates Reciprocal TGF-beta 1-Integrin Crosstalk to Protect from Influenza Virus Infection[J]. PLOS PATHOGENS,2015,11(4):e1004824-e1004824.
APA	Li, CY.,Jiao, SZ.,Wang, GJ.,Gao, YZ.,Liu, C.,...&Wang, HY.(2015).The Immune Adaptor ADAP Regulates Reciprocal TGF-beta 1-Integrin Crosstalk to Protect from Influenza Virus Infection.PLOS PATHOGENS,11(4),e1004824-e1004824.
MLA	Li, CY,et al."The Immune Adaptor ADAP Regulates Reciprocal TGF-beta 1-Integrin Crosstalk to Protect from Influenza Virus Infection".PLOS PATHOGENS 11.4(2015):e1004824-e1004824.