Ablation of IL-17A abrogates progression of spontaneous intestinal tumorigenesis

Wook Jin Chae, Thomas F. Gibson, Daniel Zelterman, Liming Hao, Octavian Henegariu, Alfred L.M. Bothwell

Research output: Contribution to journalArticlepeer-review

191 Scopus citations

Abstract

The intrinsic role of endogenous IL-17A in spontaneous intestinal tumorigenesis has not been addressed previously to our knowledge. Ablation of IL-17A significantly reduced tumor development in mice bearing a heterozygote mutation in the adenomatous polyposis coli (APC) gene (ApcMin/+ mice). There was also a decrease in inflammatory cytokines and proinflammatory mediators, reduced infiltration of lymphocytes including T cells, and preservation of intestinal architecture and the presence of APC protein in intestinal epithelial cells. Interestingly, IL-17A ablation also corrected immunological abnormalities such as splenomegaly and thymic atrophy in Apc Min/+ mice. CD4 T cells from ApcMin/+ mice showed hyperproliferative potential in vitro and in vivo and increased levels of IL-17A and IL-10. The effector CD4 T cells from ApcMin/+ mice were more resistant to regulatory T cell-mediated suppression. Finally, these CD4 T cells induced colitis in immunodeficient mice upon adoptive transfer, whereas the ablation of IL-17A in CD4 T cells in ApcMin/+ mice completely abolished this pathogenic potential in vivo. Taken together, our results show that CD4 T cell-derived IL-17A promotes spontaneous intestinal tumorigenesis with altered functions of CD4 T cells in ApcMin/+ mice.

Original languageEnglish (US)
Pages (from-to)5540-5544
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number12
DOIs
StatePublished - Mar 23 2010
Externally publishedYes

Keywords

  • Colon cancer
  • Inflammation
  • T cells

ASJC Scopus subject areas

  • General

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