| First Author | Chae WJ | Year | 2015 |
| Journal | J Immunol Res | Volume | 2015 |
| Pages | 860106 | PubMed ID | 26146642 |
| Mgi Jnum | J:316516 | Mgi Id | MGI:6837915 |
| Doi | 10.1155/2015/860106 | Citation | Chae WJ, et al. (2015) Spontaneous Intestinal Tumorigenesis in Apc (/Min+) Mice Requires Altered T Cell Development with IL-17A. J Immunol Res 2015:860106 |
| abstractText | 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, Apc (flox/+) 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 naive 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. |
