Deficiency of the immunostimulatory cytokine IL-21 promotes intestinal neoplasia via dysregulation of the Th1/Th17 axis.

ABSTRACT: IL-21 has reported activity in promoting both Th1 and Th17 immune responses. Its role in sporadic human colorectal cancer is unknown. We aimed to delineate the role of IL-21 in a model of sporadic intestinal carcinogenesis. We found that in APC^MIN/+ mice, ablation of IL-21 increased intestinal tumorigenesis. Expression of pro-inflammatory Th17-associated genes, including ROR?t and IL-17A, was increased in the intestine in the absence of IL-21, while expression of antitumor Th1-associated genes Tbet, IFN?, granzyme B, and perforin was decreased. Similarly, the IL-21-deficient APC^MIN/+ mouse intestines had fewer infiltrating T cells as well as decreased effector memory T cells, NK cells, and granzyme B-expressing cells. Finally, our data suggest that IL-21 impairs Th17 immune responses as mesenteric lymph nodes from IL-21-deficient mice had increased IL-17A expression, and naive helper T cells from IL-21-deficient mice were more prone to differentiate into IL-17A-secreting cells.

SUBMITTER: Shapiro M 

PROVIDER: S-EPMC5283644 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature