IL-17F deficiency inhibits small intestinal tumorigenesis in ApcMin/+ mice

Abstract

IL-17 plays an important role in gut homeostasis. However, the role of IL-17F in intestinal tumorigenesis has not been addressed. Here we demonstrate that ablation of IL-17F significantly inhibits spontaneous intestinal tumorigenesis in the small intestine of Apc(Min/+) mice. IL-17F ablation decreased IL-1β and Cox-2 expression as well as IL-17 receptor C (IL-17RC) expression, which were increased in tumors from Apc(Min/+) mice. Lack of IL-17F did not reverse the splenomegaly but partially restored thymic atrophy, suggesting a local effect of IL-17F in the intestine. IL-17F deficient Apc(Min/+) mice showed a significant decrease in immune cell infiltration in the lamina propria. Interestingly, the expression of IL-17A from CD4 T cells in the lamina propria remains unchanged in the absence of IL-17F. Collectively, our results suggest the proinflammatory and essential role of IL-17F to develop spontaneous intestinal tumorigenesis in Apc(Min/+) mice in the presence of IL-17A.