Spontaneous intestinal tumorigenesis in Apc/Min+ mice requires altered t cell development with IL-17A

Wook Jin Chae, Alfred L.M. Bothwell

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

The control of inflammatory diseases requires functional regulatory T cells (Tregs) with significant Gata-3 expression. Here we address the inhibitory role of Tregs on intestinal tumorigenesis in the Apc/Min+ mouse model that resembles human familial adenomatous polyposis (FAP). Apc/Min+ mice had a markedly increased frequency of Foxp3+ Tregs and yet decreased Gata-3 expression in the lamina propria. To address the role of heterozygous Apc gene mutation in Tregs, we generated Foxp3-Cre, Apcflox/+ mice. Tregs from these mice effectively inhibited tumorigenesis comparable to wild type Tregs after adoptive transfer into Apc/Min+ mice, demonstrating that the heterozygous Apc gene mutation in Tregs does not induce the loss of control over tumor microenvironment. Adoptive transfer of in vitro generated Apc/Min+ iTregs (inducible Tregs) failed to inhibit intestinal tumorigenesis, suggesting that naïve CD4 T cells generated from Apc/Min+ mice thymus were impaired. We also showed that adoptively transferred IL-17A-deficient Apc/Min+ Tregs inhibited tumor growth, suggesting that IL-17A was critical to impair the tumor regression function of Apc/Min+ Tregs. Taken together, our results suggest that both T cell development in a functional thymus and IL-17A control the ability of Treg to inhibit intestinal tumorigenesis in Apc/Min+ mice.

Original languageEnglish (US)
Article number860106
JournalJournal of Immunology Research
Volume2015
DOIs
StatePublished - 2015
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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