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Journal of Immunology Research
Volume 2015, Article ID 860106, 11 pages
Research Article

Spontaneous Intestinal Tumorigenesis in Mice Requires Altered T Cell Development with IL-17A

Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA

Received 17 December 2014; Revised 6 May 2015; Accepted 6 May 2015

Academic Editor: David E. Gilham

Copyright © 2015 Wook-Jin Chae and Alfred L. M. Bothwell. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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 mouse model that resembles human familial adenomatous polyposis (FAP). 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 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 iTregs (inducible Tregs) failed to inhibit intestinal tumorigenesis, suggesting that naïve CD4 T cells generated from mice thymus were impaired. We also showed that adoptively transferred IL-17A-deficient Tregs inhibited tumor growth, suggesting that IL-17A was critical to impair the tumor regression function of 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 mice.