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

Article English OPEN
Yuanyuan Wang ; Xuefeng Jiang ; Junfeng Zhu ; Dan Yue ; Xiaoqing Zhang ; Xiao Wang ; Yong You ; Biao Wang ; Ying Xu ; Changlong Lu ; Xun Sun ; Yasunobu Yoshikai (2016)
  • Publisher: Nature Publishing Group
  • Journal: Scientific Reports, volume 6 (issn: 2045-2322, eissn: 2045-2322)
  • Related identifiers: pmc: PMC4992961, doi: 10.1038/srep31881
  • Subject: Article

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.
Share - Bookmark