Cutting Edge: STING Mediates Protection against Colorectal Tumorigenesis by Governing the Magnitude of Intestinal Inflammation

被引:129
作者
Zhu, Qifan [1 ,2 ]
Man, Si Ming [1 ]
Gurung, Prajwal [1 ]
Liu, Zhiping [1 ]
Vogel, Peter [3 ]
Lamkanfi, Mohamed [4 ,5 ]
Kanneganti, Thirumala-Devi [1 ]
机构
[1] St Jude Childrens Res Hosp, Dept Immunol, Memphis, TN 38105 USA
[2] Univ Tennessee, Ctr Hlth Sci, Integrated Biomed Sci Program, Memphis, TN 38163 USA
[3] St Jude Childrens Res Hosp, Vet Pathol Core, Memphis, TN 38105 USA
[4] Flemish Inst Biotechnol, Dept Med Prot Res, B-9000 Ghent, Belgium
[5] Univ Ghent, Dept Biochem, B-9000 Ghent, Belgium
基金
欧洲研究理事会; 美国国家卫生研究院;
关键词
INNATE IMMUNE SENSOR; INTRACELLULAR DNA; NLRP3; INFLAMMASOME; NUCLEIC-ACIDS; BACTERIAL RNA; TUMOR-CELLS; CANCER; SURVIVAL; STAT3; ACTIVATION;
D O I
10.4049/jimmunol.1402051
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Stimulator of IFN genes (STING) is a cytoplasmic innate immune sensor for cyclic dinucleotides that also serves a dual role as an adaptor molecule for a number of intracellular DNA receptors. Although STING has important functions in the host defense against pathogens and autoimmune diseases, its physiological role in cancer is unknown. In this study, we show that STING-deficient mice are highly susceptible to colitis-associated colorectal cancer. Colons of STING-deficient mice exhibit significant intestinal damage and overt proliferation during early stages of tumorigenesis. Moreover, STING-deficient mice fail to restrict activation of the NF-kappa B- and STAT3-signaling pathways, which leads to increased levels of the proinflammatory cytokines IL-6 and KC. Therefore, our results identified an unexpected and important role for STING in mediating protection against colorectal tumorigenesis.
引用
收藏
页码:4779 / 4782
页数:4
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