期刊
NATURE MEDICINE
卷 15, 期 9, 页码 1016-U64出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nm.2015
关键词
-
资金
- Crohn's and Colitis Foundation [RO1 DK45496, RO1 DK080817]
- US National Institutes of Health
- Special Projects of Research Excellence [CA62924, R24 DK64388, RR00171]
- Institutional Training for Pediatricians [5 T32 HD44355]
- Clinical Pharmacology [2 T32GM066691]
- [F32 DK079509]
- EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT [T32HD044355] Funding Source: NIH RePORTER
- NATIONAL CANCER INSTITUTE [P50CA062924] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR RESEARCH RESOURCES [K26RR000171] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI089830] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R24DK064388, R01DK045496, R01DK080817, F32DK079509] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [T32GM066691] Funding Source: NIH RePORTER
The intestinal flora may promote colon tumor formation. Here we explore immunologic mechanisms of colonic carcinogenesis by a human colonic bacterium, enterotoxigenic Bacteroides fragilis (ETBF). ETBF that secretes B. fragilis toxin (BFT) causes human inflammatory diarrhea but also asymptomatically colonizes a proportion of the human population. Our results indicate that whereas both ETBF and nontoxigenic B. fragilis (NTBF) chronically colonize mice, only ETBF triggers colitis and strongly induces colonic tumors in multiple intestinal neoplasia (Min) mice. ETBF induces robust, selective colonic signal transducer and activator of transcription-3 (Stat3) activation with colitis characterized by a selective T helper type 17 (T(H)17) response distributed between CD4(+) T cell receptor-alpha beta (TCR alpha beta)(+) and CD4(-)8(-)TCR gamma alpha(+) T cells. Antibody-mediated blockade of interleukin-17 (IL-17) as well as the receptor for IL-23, a key cytokine amplifying T(H)17 responses, inhibits ETBF-induced colitis, colonic hyperplasia and tumor formation. These results show a Stat3- and T(H)17-dependent pathway for inflammation-induced cancer by a common human commensal bacterium, providing new mechanistic insight into human colon carcinogenesis.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据