期刊
CANCER LETTERS
卷 493, 期 -, 页码 102-112出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2020.08.007
关键词
Colorectal cancer; Plasmacytoid dendritic cell; Myeloid-derived suppressor cell; Toll-like receptor
类别
资金
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Science, ICT, and Future Planning [NRF-2017M3A9C8060390, NRF-2017R1A6A3A11031757]
Toll-like receptor (TLR)3 and TLR7 are important for stimulating plasmacytoid dendritic cells (pDCs), which secrete type I interferon. Mice deficient for TLR3 and TLR7 (TLR3(-/-)TLR7(-/-)) reportedly exhibit deteriorated colitis because of impaired pDCs. However, the role of pDCs in tumorigenesis-associated inflammation progression has not been studied. We treated wild-type or TLR3(-/-)TLR7(-/-) mice with dextran sulfate sodium (DSS) and/or azoxymethane (AOM) and examined colon mucosa, measured body weight and colon length of mice, and examined pDC and myeloid-derived suppressor cell (MDSC) accumulation. Further, we depleted pDCs in AOM/DSS-treated wild-type mice by treating them with anti-PDCA-1 antibodies. We found that MDSCs significantly increased, while pDCs decreased in TLR3(-/-)TLR7(-/-) mice. Moreover, TLR3(-/-)TLR7(-/-) mice developed colitis-associated colon cancer following AOM/DSS treatment. Additionally, we showed that a defect in TLR7 of pDCs is responsible for the aggravation of colitis-associated colon cancer. Further, we showed that TLR7 ligand mitigates colitis-associated colon cancer. Collectively, our results demonstrate that gut pDCs play a crucial role in reducing colorectal cancer development via the regulation of infiltrating MDSCs.
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