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

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, Catherine Blackburn, Yina H. Huang, Thomas A. Hamilton, Bing Su, Xiaoxia Li

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)3849-3857
Number of pages10
JournalJournal of Immunology
Volume199
Issue number11
Early online date25 Oct 2017
DOIs
Publication statusPublished - 1 Dec 2017

Keywords

  • IL-17A
  • colon cancer
  • tissue repair
  • inflammation

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