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

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

Journal of immunology (Baltimore, Md. : 1950) (2017-10-27)

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

PMID29070673

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.

MATERIALS

Product Number

Brand

Product Description

SML2355

Sigma-Aldrich

BIX02189, ≥98% (HPLC)