title: 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 APCMIN/+mice, ablation of IL-21 increased intestinal tumorigenesis. Expression of pro-inflammatory Th17-associated genes, includingRORγtandIL-17A, was increased in the intestine in the absence of IL-21, while expression of antitumor Th1-associated genesTbet, IFNγ, granzyme B, andperforinwas decreased. Similarly, the IL-21-deficient APCMIN/+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 increasedIL-17Aexpression, and naive helper T cells from IL-21-deficient mice were more prone to differentiate into IL-17A-secreting cells.
authors.affiliation: Research Services, VA Boston Healthcare System, West Roxbury, MA, USA; Harvard Medical School, Boston, MA, USA.
authors.forename: Mia
authors.initials: M
authors.lastname: Shapiro
authors.affiliation: Research Services, VA Boston Healthcare System, West Roxbury, MA, USA; Harvard Medical School, Boston, MA, USA.
authors.forename: Bisweswar
authors.initials: B
authors.lastname: Nandi
authors.affiliation: Research Services, VA Boston Healthcare System, West Roxbury, MA, USA; Harvard Medical School, Boston, MA, USA.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Gonzalez
authors.affiliation: Research Services, VA Boston Healthcare System, West Roxbury, MA, USA; Harvard Medical School, Boston, MA, USA; Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Rao H
authors.initials: RH
authors.lastname: Prabhala
authors.affiliation: Harvard Medical School, Boston, MA, USA; Medicine Services, VA Boston Healthcare System, West Roxbury, MA, USA; Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mashimo
authors.affiliation: Harvard Medical School, Boston, MA, USA; Pathology Services, VA Boston Healthcare System, West Roxbury, MA, USA.
authors.forename: Qin
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Harvard Medical School, Boston, MA, USA; Medicine Services, VA Boston Healthcare System, West Roxbury, MA, USA; Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Natasha Y
authors.initials: NY
authors.lastname: Frank
authors.affiliation: Harvard Medical School, Boston, MA, USA; Dana-Farber Cancer Institute, Boston, MA, USA; Medicine Services, VA Boston Healthcare System, West Roxbury, MA, USA.
authors.forename: Nikhil C
authors.initials: NC
authors.lastname: Munshi
authors.affiliation: Harvard Medical School, Boston, MA, USA; Brigham and Women's Hospital, Boston, MA, USA; Surgery Services, VA Boston Healthcare System, West Roxbury, MA, USA.
authors.forename: Jason S
authors.initials: JS
authors.lastname: Gold
keywords: Adenoma; IL-21; Th1 cells; Th17 cells; carcinogenesis; colorectal neoplasms; mice