| First Author | Hong EH | Year | 2020 |
| Journal | Cancer Lett | Volume | 493 |
| Pages | 102-112 | PubMed ID | 32810576 |
| Mgi Jnum | J:296655 | Mgi Id | MGI:6467622 |
| Doi | 10.1016/j.canlet.2020.08.007 | Citation | Hong EH, et al. (2020) Plasmacytoid dendritic cells regulate colitis-associated tumorigenesis by controlling myeloid-derived suppressor cell infiltration. Cancer Lett 493:102-112 |
| abstractText | 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. |
