IL-17A–Induced PLET1 Expression Contributes to Tissue Repair and Colon Tumorigenesis

作者：Jarod A. Zepp, Junjie Zhao, Caini Liu, Katazyna Bulek, Ling Wu, Xing Chen, Yujun Hao, Zhenghe Wang, Xinxin Wang, Wenjun Ouyang, Matthew F. Kalady, Julie Carman, Wen-Pin Yang, Jun Zhu, Clare Blackburn, Yina H. Huang, Thomas A. Hamilton, Bing Su, Xiaoxia Li · 发表于：The Journal of Immunology · 年份：2017 · DOI：10.4049/jimmunol.1601540 · 被引用次数：69 · 研究领域：Digestive system and related health、Genetic factors in colorectal cancer、Cancer Cells and Metastasis

Abstract This study identifies a novel mechanism linking IL-17A with colon tissue repair and tumor development. Abrogation of IL-17A signaling in mice attenuated tissue repair of dextran sulfate sodium (DSS)-induced damage in colon epithelium and markedly reduced tumor development in an azoxymethane/DSS model of colitis-associated cancer. A novel IL-17A target gene, PLET1 (a progenitor cell marker involved in wound healing), was highly induced in DSS-treated colon tissues and tumors in an IL-17RC–dependent manner. PLET1 expression was induced in LGR5+ colon epithelial cells after DSS treatment. LGR5+PLET1+ marks a highly proliferative cell population with enhanced expression of IL-17A target genes. PLET1 deficiency impaired tissue repair of DSS-induced damage in colon epithelium and reduced tumor formation in an azoxymethane/DSS model of colitis-associated cancer. Our results suggest that IL-17A–induced PLET1 expression contributes to tissue repair and colon tumorigenesis.