IL-21/IL-21R signaling suppresses intestinal inflammation induced by DSS through regulation of Th responses in lamina propria in mice

Yuanyuan Wang, Xuefeng Jiang, Junfeng Zhu, Dan Yue, Xiaoqing Zhang, Xiao Wang, Yong You, Biao Wang, Ying Xu, Changlong Lu, Xun Sun, Yasunobu Yoshikai

    Research output: Contribution to journalArticlepeer-review

    11 Citations (Scopus)

    Abstract

    Serum level of IL-21 is increased in patients with inflammatory bowel diseases (IBD), suggesting that IL-21/IL-21 receptor (IL-21R) signaling may be involved in the pathogenesis of IBD. However, the role of IL-21/IL-21 receptor signaling plays in the pathogenesis of IBD is not very clear. In this study, using IL-21R.KO mice, we tested the role of IL-21/IL-21R signaling in the regulation of T helper cell responses during intestinal inflammation. Here we found that IL-21R.KO mice were more susceptible to DSS-induced colitis as compared with C57BL/6 mice. The spontaneous inflammatory cytokines released by macrophages in LP of colon were significantly increased, and Th2, Th17 and Treg responses were down-regulated markedly. However, Th1 responses were significantly up-regulated in IL-21R.KO mice. Meanwhile, the population of CD8+ CD44+ IFN-γ + T cells was markedly elevated in LP of inflammatory intestine of IL-21RKO mice. In vivo, after disease onset, DSS-induced intestinal inflammation was ameliorated in C57BL/6 mice treated with rIL-21. Our results demonstrate that IL-21/IL-21R signaling contributes to protection against DSS-induced acute colitis through suppression of Th1 and activation of Th2, Th17 and Treg responses in mice. Therefore, therapeutic manipulation of IL-21/IL-21R activity may allow improved immunotherapy for IBD and other inflammatory diseases associated with Th cell responses.

    Original languageEnglish
    Article number31881
    JournalScientific reports
    Volume6
    DOIs
    Publication statusPublished - Aug 22 2016

    All Science Journal Classification (ASJC) codes

    • General

    Fingerprint Dive into the research topics of 'IL-21/IL-21R signaling suppresses intestinal inflammation induced by DSS through regulation of Th responses in lamina propria in mice'. Together they form a unique fingerprint.

    Cite this