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

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

Oncoimmunology. 2017;6(1):e1261776

Authors: Shapiro M, Nandi B, Gonzalez G, Prabhala RH, Mashimo H, Huang Q, Frank NY, Munshi NC, Gold JS

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 RORγt and IL-17A, was increased in the intestine in the absence of IL-21, while expression of antitumor Th1-associated genes Tbet, IFNγ, 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.

PMID: 28197386 [PubMed - in process]

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