TIPE2 Controls Innate Immunity to RNA by Targeting the Phosphatidylinositol 3-Kinase-Rac Pathway

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	TIPE2 Controls Innate Immunity to RNA by Targeting the Phosphatidylinositol 3-Kinase-Rac Pathway
	Sun, Honghong ; Zhuang, Guohong ; Chai, Lihui ; Wang, Zhaojun ; Johnson, Derek ; Ma, Yuanfang ; Chen, Youhai H. ; Zhuang GH(庄国洪)
刊名	http://dx.doi.org/10.4049/jimmunol.1103477
	2012-09-15
关键词	DOUBLE-STRANDED-RNA DOMAIN-CONTAINING ADAPTER IFN-BETA PROMOTER NF-KAPPA-B RHO-GTPASES REGULATORY FACTOR-3 ACTIVATION RAC RECOGNITION ROLES
英文摘要	National Institutes of Health [AI-077533, AI-050059, GM-085112]; RNA receptors such as TLR3 and retinoid acid-inducible gene I/melanoma differentiation-associated gene 5 play essential roles in innate immunity to RNA viruses. However, how innate immunity to RNAs is controlled at the molecular level is not well understood. We describe in this study a new regulatory pathway of anti-RNA immunity that is composed of PI3K, its target GTPase Rac, and the newly described immune regulator TNF-alpha-induced protein 8 like-2 (TIPE2, or TNFAIP8L2). Polyinosinic-polycytidylic acid [Poly (I: C)], a dsRNA receptor ligand, activates Rac via its guanine nucleotide exchange factor Tiam; this leads to the activation of cytokine genes and, paradoxically, downregulation of the Tipe2 gene. TIPE2 is a negative regulator of immunity; its deficiency leads to hyperactivation of the PI3K-Rac pathway as exemplified by enhanced AKT, Rac, P21-activated kinase, and IFN regulatory factor 3 activities. As a consequence, TIPE2 knockout myeloid cells are hyperreactive to Poly (I:C) stimulation, and TIPE2 knockout mice are hypersensitive to Poly (I:C)-induced lethality. These results indicate that TIPE2 controls innate immunity to RNA by targeting the PI3K-Rac pathway. Therefore, manipulating TIPE2 or Rac functions can be effective for controlling RNA viral infections. The Journal of Immunology, 2012, 189: 2768-2773.
语种	英语
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/71343]
专题	医学院－已发表论文
推荐引用方式 GB/T 7714	Sun, Honghong,Zhuang, Guohong,Chai, Lihui,et al. TIPE2 Controls Innate Immunity to RNA by Targeting the Phosphatidylinositol 3-Kinase-Rac Pathway[J]. http://dx.doi.org/10.4049/jimmunol.1103477,2012.
APA	Sun, Honghong.,Zhuang, Guohong.,Chai, Lihui.,Wang, Zhaojun.,Johnson, Derek.,...&庄国洪.(2012).TIPE2 Controls Innate Immunity to RNA by Targeting the Phosphatidylinositol 3-Kinase-Rac Pathway.http://dx.doi.org/10.4049/jimmunol.1103477.
MLA	Sun, Honghong,et al."TIPE2 Controls Innate Immunity to RNA by Targeting the Phosphatidylinositol 3-Kinase-Rac Pathway".http://dx.doi.org/10.4049/jimmunol.1103477 (2012).