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- Title
A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses.
- Authors
Shaoguang Wu; Rhee, Ki-Jong; Albesiano, Emilia; Rabizadeh, Shervin; Xinqun Wu; Hung-Rong Yen; Huso, David L.; Brancati, Frederick L.; Wick, Elizabeth; McAllister, Florencia; Housseau, Franck; Pardoll, Drew M.; Sears, Cynthia L.
- Abstract
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 (TH17) response distributed between CD4+ T cell receptor-αβ (TCRαβ)+ and CD4–8–TCRγδ+ T cells. Antibody-mediated blockade of interleukin-17 (IL-17) as well as the receptor for IL-23, a key cytokine amplifying TH17 responses, inhibits ETBF-induced colitis, colonic hyperplasia and tumor formation. These results show a Stat3- and TH17-dependent pathway for inflammation-induced cancer by a common human commensal bacterium, providing new mechanistic insight into human colon carcinogenesis.
- Publication
Nature Medicine, 2009, Vol 15, Issue 9, p1016
- ISSN
1078-8956
- Publication type
Academic Journal
- DOI
10.1038/nm.2015