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

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. © 2015 wook-jin chae and alfred l. m. bothwell.