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 journalArticle

    4 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

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    Interleukin-21 Receptors
    Mucous Membrane
    Inflammation
    Inflammatory Bowel Diseases
    Colitis
    Inbred C57BL Mouse
    interleukin-21
    Helper-Inducer T-Lymphocytes
    Immunotherapy
    Intestines
    Colon
    Macrophages

    All Science Journal Classification (ASJC) codes

    • General

    Cite this

    IL-21/IL-21R signaling suppresses intestinal inflammation induced by DSS through regulation of Th responses in lamina propria in mice. / Wang, Yuanyuan; Jiang, Xuefeng; Zhu, Junfeng; Yue, Dan; Zhang, Xiaoqing; Wang, Xiao; You, Yong; Wang, Biao; Xu, Ying; Lu, Changlong; Sun, Xun; Yoshikai, Yasunobu.

    In: Scientific reports, Vol. 6, 31881, 22.08.2016.

    Research output: Contribution to journalArticle

    Wang, Y, Jiang, X, Zhu, J, Yue, D, Zhang, X, Wang, X, You, Y, Wang, B, Xu, Y, Lu, C, Sun, X & Yoshikai, Y 2016, 'IL-21/IL-21R signaling suppresses intestinal inflammation induced by DSS through regulation of Th responses in lamina propria in mice', Scientific reports, vol. 6, 31881. https://doi.org/10.1038/srep31881
    Wang, Yuanyuan ; Jiang, Xuefeng ; Zhu, Junfeng ; Yue, Dan ; Zhang, Xiaoqing ; Wang, Xiao ; You, Yong ; Wang, Biao ; Xu, Ying ; Lu, Changlong ; Sun, Xun ; Yoshikai, Yasunobu. / IL-21/IL-21R signaling suppresses intestinal inflammation induced by DSS through regulation of Th responses in lamina propria in mice. In: Scientific reports. 2016 ; Vol. 6.
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    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.",
    author = "Yuanyuan Wang and Xuefeng Jiang and Junfeng Zhu and Dan Yue and Xiaoqing Zhang and Xiao Wang and Yong You and Biao Wang and Ying Xu and Changlong Lu and Xun Sun and Yasunobu Yoshikai",
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    AU - Zhang, Xiaoqing

    AU - Wang, Xiao

    AU - You, Yong

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