Alterations in the Microbiota Drive Interleukin-17C Production from Intestinal Epithelial Cells to Promote Tumorigenesis

被引：221

作者：

Song, Xinyang ^{[1
,2
]}

Gao, Hanchao ^{[1
,2
]}

Lin, Yingying ^{[1
,2
]}

Yao, Yikun ^{[1
,2
]}

Zhu, Shu ^{[1
,2
]}

Wang, Jingjing ^{[1
,2
]}

Liu, Yan ^{[1
,2
]}

Yao, Xiaomin ^{[4
,5
]}

Meng, Guangxun ^{[4
,5
]}

Shen, Nan ^{[1
,2
,3
]}

Shi, Yufang ^{[1
,2
]}

Iwakura, Yoichiro ^{[6
]}

Qian, Youcun ^{[1
,2
,3
]}

机构：

[1] Chinese Acad Sci, Key Lab Stem Cell Biol, Inst Hlth Sci, Shanghai Inst Biol Sci, Shanghai 200025, Peoples R China

[2] Shanghai Jiao Tong Univ, Sch Med, Shanghai 200025, Peoples R China

[3] Shanghai Jiao Tong Univ, Sch Med, Shanghai Renji Hosp, Shanghai Inst Rheumatol, Shanghai 200001, Peoples R China

[4] Shanghai Inst Biol Sci, Inst Pasteur Shanghai, Key Lab Mol Virol & Immunol, Shanghai 200025, Peoples R China

[5] Chinese Acad Sci, Shanghai 200025, Peoples R China

[6] Tokyo Univ Sci, Res Inst Biomed Sci, Noda, Chiba 2780022, Japan

来源：

IMMUNITY | 2014年 / 40卷 / 01期

基金：

中国国家自然科学基金;

关键词：

COLITIS-ASSOCIATED CANCER; COLORECTAL-CANCER; AUTOIMMUNE-DISEASE; IMMUNE-SYSTEM; INFLAMMATION; RECEPTOR; NEOPLASIA; ACTIVATION; IL-17C; HOMEOSTASIS;

D O I：

10.1016/j.immuni.2013.11.018

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

Although the microbiota has been shown to drive production of interleukin-17A (IL-17A) from T helper 17 cells to promote cell proliferation and tumor growth in colorectal cancer, the molecular mechanisms for microbiota-mediated regulation of tumorigenesis are largely unknown. Here, we found that the innate-like cytokine IL-17C was upregulated in human colorectal cancers and in mouse intestinal tumor models. Alterations in the microbiota drove IL-17C upregulation specifically in intestinal epithelial cells (IECs) through Toll-like receptor (TLR)-MyD88-dependent signaling during intestinal tumorigenesis. Microbiota-driven IL-17C induced Bcl-2 and Bcl-x(L) expression in IECs in an autocrine manner to promote cell survival and tumorigenesis in both chemically induced and spontaneous intestinal tumor models. Thus, IL-17C promotes cancer development by increasing IEC survival, and the microbiota can mediate cancer pathogenesis through regulation of IL-17C.

引用

页码：140 / 152

页数：13

共 41 条

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Intestinal Inflammation Targets Cancer-Inducing Activity of the Microbiota [J].