Alterations in the Microbiota Drive Interleukin-17C Production from Intestinal Epithelial Cells to Promote Tumorigenesis
| Autor: | Guangxun Meng, Yufang Shi, Gao Hanchao, Youcun Qian, Yingying Lin, Yikun Yao, Yoichiro Iwakura, Xiaomin Yao, Xinyang Song, Yan Liu, Jingjing Wang, Nan Shen, Shu Zhu |
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| Rok vydání: | 2014 |
| Předmět: |
Colorectal cancer
Carcinogenesis Cell Survival medicine.medical_treatment Immunology bcl-X Protein Biology medicine.disease_cause digestive system Mice Downregulation and upregulation medicine Animals Humans Immunology and Allergy Intestinal Mucosa Autocrine signalling Cells Cultured Mice Knockout Cell growth Microbiota Interleukin-17 Interleukin medicine.disease Cell biology Up-Regulation Autocrine Communication Disease Models Animal Cytokine Infectious Diseases Proto-Oncogene Proteins c-bcl-2 Colonic Neoplasms Myeloid Differentiation Factor 88 Signal transduction Signal Transduction |
| Zdroj: | Immunity. 40(1):140-152 |
| ISSN: | 1074-7613 |
| DOI: | 10.1016/j.immuni.2013.11.018 |
| Popis: | SummaryAlthough 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-xL 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. |
| Databáze: | OpenAIRE |
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