Role of interleukin-21 isoform in dextran sulfate sodium (DSS)-induced colitis

Araki, Akemi; Nara, Hidetoshi; Rahman, Mizanur; Onoda, Tadashi; Li, Jun; Juliana, Farha Matin; Jin, Lianjin; Murata, Kazuko; Takeda, Yuji; Asao, Hironobu

doi:10.1016/j.cyto.2013.03.006

Cited by 18 publications

(16 citation statements)

References 37 publications

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“…However, a recent study showed that Treg cells responses were upregulated in the DSS-induced colitis in mIL-21iso-Tg mice50. In this study, Treg cells significantly decreased in IL21RKO mice with DSS-induced colitis.…”

Section: Discussioncontrasting

confidence: 44%

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

Wang

Jiang

Zhu

et al. 2016

Sci Rep

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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.

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Section: Discussioncontrasting

confidence: 44%

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

Wang

Jiang

Zhu

et al. 2016

Sci Rep

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“…A partial protection from DSS-induced colitis has been previously reported in complete, non-tissue specific IL-21 deficient mice 56 . We believe that the differences on the role of IL-21 on DSS-induced colitis (protective in our work versus pathogenic in 56 ) might reflect differential effects of IL-21 on ILCs and CD4+ T cells and the absence of ILCs in RAG2/IL2RG mice.…”

Section: Discussionmentioning

confidence: 67%

“…We believe that the differences on the role of IL-21 on DSS-induced colitis (protective in our work versus pathogenic in 56 ) might reflect differential effects of IL-21 on ILCs and CD4+ T cells and the absence of ILCs in RAG2/IL2RG mice. Alternatively, these different outcomes might result from the use of IL-21 deficient mice in the work of Araki et al 56 , instead of the IL-21R KO mice used in our studies.…”

Section: Discussionmentioning

confidence: 70%

IL-21 induces IL-22 production in CD4+ T cells

et al. 2014

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IL-22 produced by innate lymphoid cells (ILCs) and CD4+ T cells plays an important role in host defense and mucosal homeostasis, thus it is important to investigate the mechanisms that regulate IL-22 production. We investigated the regulation IL-22 production by CD4+ T cells. Here we show that IL-21 triggers IL-22, but not IL-17 production by CD4+ T cells. STAT3, activated by IL-21, controls the epigenetic status of the il22 promoter and its interaction with the aryl hydrocarbon receptor (AhR). Moreover, IL-21 and AhR signaling in T cells control IL-22 production and the development of dextran sodium sulfate-induced colitis in ILC-deficient mice. Thus, we have identified IL-21 as an inducer of IL-22 production in CD4+ T cells in vitro and in vivo.

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“…The DSS mouse model of acute colitis is well-characterized by increased epithelial injury in previous work [2]–[5], and it has been proved that BBR has influence on promoting the recovery of DSS-treated colitis [1]. To confirm the efficiency of anti-inflammatory effects of CK and explore its functional mechanism, mice were treated with DSS for 4 days to induce mild colitis, and then CK was administered via intraperitoneal injection for the following 3 days recovery (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Evidence from immunological, microbiological, and genetic studies suggest that IBD results from dysregulation of the mucosal immune system leading to excessive immunological responses to intestinal microflora, or changes in the composition of intestinal microflora and/or deranged epithelial barrier function that elicits pathological responses from the normal mucosal immune system in genetically susceptible hosts [1]–[5]. Nevertheless, acute intestinal inflammation is usually followed by physiologic healing of the damaged tissue and restoration of the normal structure and function of the intestine [6].…”

Section: Introductionmentioning

confidence: 99%

Ginsenoside Metabolite Compound K Promotes Recovery of Dextran Sulfate Sodium-Induced Colitis and Inhibits Inflammatory Responses by Suppressing NF-κB Activation

Zhong

Wang

et al. 2014

PLoS ONE

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Phytogenic compounds with anti-oxidant and anti-inflammatory properties, such as ginsenoside metabolite compound K (CK) or berberine (BBR), are currently discussed as promising complementary agents in the prevention and treatment of cancer and inflammation. The latest study showed that ginsenoside Rb1 and its metabolites could inhibit TNBS-induced colitis injury. However, the functional mechanisms of anti-inflammation effects of ginsenoside, particularly its metabolite CK are still not clear. Here, using dextran sulfate sodium (DSS)-induced colitis in mice, clinical parameters, intestinal integrity, pro-inflammatory cytokines production, and signaling pathways in colonic tissues were determined. In mild and sever colitis mice, CK and BBR (as a positive agent) alleviated colitis histopathology injury, ameliorated myeloperoxidase (MPO) activity, reduced pro-inflammatory cytokines production, such as, IL-6, IL-1β, TNF-α, and increased anti-inflammatory cytokine IL-10 production in both mice colon tissues and blood. Nevertheless, the results revealed that CK and BBR inhibited NF-κB p65 nuclear translocation, downregulated p-IκBα and upregulated IκBα, indicating that CK, as well as BBR, suppressed the activation of the NF-κB pathway in the progression of colitis with immunofluorescence, immunohistochemical and western blotting analysis. Furthermore, CK inhibited pro-inflammatory cytokines production in LPS-activated macrophages via down-regulation of NF-κB signaling pathway. Taken together, our results not only reveal that CK promotes the recovery of the progression of colitis and inhibits the inflammatory responses by suppressing NF-κB activation, but also suggest that CK downregulates intestinal inflammation through regulating the activation of macrophages and pro-inflammatory cytokines production.

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Role of interleukin-21 isoform in dextran sulfate sodium (DSS)-induced colitis

Cited by 18 publications

References 37 publications

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

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

IL-21 induces IL-22 production in CD4+ T cells

Ginsenoside Metabolite Compound K Promotes Recovery of Dextran Sulfate Sodium-Induced Colitis and Inhibits Inflammatory Responses by Suppressing NF-κB Activation

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