Regulation of Gut Inflammation and Th17 Cell Response by Interleukin-21

Fina, Daniele; Sarra, Massimiliano; Fantini, Massimo; Rizzo, Angelamaria; Caruso, Roberta; Caprioli, Flavio; Stolfi, Carmine; Cardolini, Iris; Dottori, Marta; Boirivant, Monica; Pallone, Francesco; MacDonald, Thomas T.; Monteleone, Giovanni

doi:10.1053/j.gastro.2008.01.041

Cited by 246 publications

(186 citation statements)

References 24 publications

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“…Excessive evidence supports that, elevated levels of IL-21 in the gut has deleterious consequences for the host. DSS or TNBS-induced wild-type colitis mice produce high level of IL-21; also IL-21-knockout mice are largely protected against disease in both models (Fina et al, 2008;Stolfi et al, 2011). IL-21 was highly expressed in human CRC patients and IL-21-deficient mice were resistant to CAC induced with AOM and DSS.…”

Section: 551 Signal Transducer and Activator Of Transcription 3 -A Pmentioning

confidence: 99%

Signal Transducer and Activator of Transcription 3 - A Promising Target in Colitis-Associated Cancer

Pandurangan¹,

Esa²

2014

Asian Pacific Journal of Cancer Prevention

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Colorectal cancer (CRC) is the third most common malignancy and fourth most common cause of cancer mortality worldwide. Untreated chronic inflammation in the intestine ranks among the top three high-risk conditions for colitis-associated colorectal cancer (CAC). Signal Transducer and Activator of Transcription 3 (STAT3) protein is a member of the STAT family of transcription factors often deregulated in CRC. In this review, we try to emphasize the critical role of STAT3 in CAC as well as the crosstalk of STAT3 with inflammatory cytokines, nuclear factor (NF)-κB, PI3K/Akt, Mammalian Target of Rapamycin (mTOR), Notch, Wnt/β-catenin and microRNA (MiR) pathways. STAT3 is considered as a primary drug target to treat CAC in humans and rodents. Also we updated the findings for inhibitors of STAT3 with regard to effeects on tumorigenesis. This review will hopefully provide insights on the use of STAT3 as a therapeutic target in CAC.

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Section: 551 Signal Transducer and Activator Of Transcription 3 -A Pmentioning

confidence: 99%

Signal Transducer and Activator of Transcription 3 - A Promising Target in Colitis-Associated Cancer

Pandurangan¹,

Esa²

2014

Asian Pacific Journal of Cancer Prevention

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“…55 Interleukin-21 Enhances IFN-c production from T cells and NK cells 60,61 Induces Th17 cells Enhances goblet cell restoration and mucus production 47 DSS, dextran sodium sulphate; G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte-macrophage colony-stimulating factor; IL-21R-Fc, interleukin-21 receptor Fc fusion protein; MMP, matrix metalloproteinase; TNBS, trinitrobenzene sulphonic acid; TNF-a, tumour necrosis factor-a.…”

Section: Interleukin-23 Has Broad Effects On Both T Cells and Non-t Cmentioning

confidence: 99%

Interleukin-23 and T helper 17-type responses in intestinal inflammation: from cytokines to T-cell plasticity

2011

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Summary Interleukin‐23 (IL‐23) plays an essential role in driving intestinal pathology in experimental models of both T‐cell‐dependent and innate colitis. Furthermore, genome‐wide association studies have identified several single‐nucleotide polymorphisms in the IL‐23 receptor (IL‐23R) gene that are associated with either susceptibility or resistance to inflammatory bowel disease in humans. Although initially found to support the expansion and maintenance of CD4+ T helper 17 (Th17) cells, IL‐23 is now recognized as having multiple effects on the immune response, including restraining Foxp3+ regulatory T‐cell activity and inducing the expression of Th17‐type cytokines from non‐T‐cell sources. Here we focus on Th17 cells and their associated cytokines IL‐17A, IL‐17F, IL‐21 and IL‐22. We review studies performed in mouse models of colitis where these effector cytokines have been shown to have either a pathogenic or a tissue‐protective function. We also discuss the heterogeneity found within the Th17 population and the phenomenon of plasticity of Th17 cells, in particular the ability of these lymphocytes to extinguish IL‐17 expression and turn on interferon‐γ production to become Th1‐like ‘ex‐Th17’ cells. Interleukin‐23 has been identified as a key driver in this process, and this may be an additional mechanism by which IL‐23 promotes pathology in the intestinal tract. These ‘ex‐Th17’ cells may contribute to disease pathogenesis through their secretion of pro‐inflammatory mediators.

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“…The identification of this new subtype of th17 cell has prompted renewed interest in IL-17 biology. IL-17 plays an important role in inflammation, and is critical in host defense against infectious disease, allergy, and autoimmune diseases such as rheumatoid arthritis and inflammatory bowel diseases, which include crohn's disease and ulcerative colitis (8,9). Interestingly, Il-17 also has been reported to be up-regulated in Helicobacter pylori (Hp) infected gastric mucosa.…”

Section: Introductionmentioning

confidence: 99%

Tumor-infiltrating CD4+ Th17 cells produce IL-17 in tumor microenvironment and promote tumor progression in human gastric cancer

Iida

Itō

Katsuda³

et al. 2011

Oncol Rep

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Abstract. recently, a subset of Il-17 producing t cells distinct from th1 or th2 cells has been described as key players in inflammation and autoimmune diseases as well as cancer development. In this study, we investigated the expression level of Il-17 and t helper 17 (th17)-related cytokines in gastric cancer tissues and assessed the association of their expression with angiogenesis and their clinicopathological parameters. tumor and adjacent normal tissues were obtained from 82 patients with gastric cancer. Il-17, Il-21 and Il-23 mRNA expression levels were quantified by real-time RT-PCR. Th17 infiltration, microvessel density and neutrophil infiltration in tumor tissues were examined by immunohistochemistry and double immunofluorescence histochemistry. Expression of IL-17, IL-21 and IL-23 mRNA was found to be significantly up-regulated in tumor tissues compared with adjacent normal tissues. the expression level of Il-17 mrnA strongly and positively correlated with that of Il-21 mrnA in tumor tissue. the number of vascular endothelial cells and infiltrating neutrophils was significantly larger in tumors expressing a high level of Il-17 mrnA than in tumors expressing a low level of Il-17 mrnA. In tumor tissues most cD4 + cells were stained with anti-Il-17 antibody. the expression level of Il-17 mrnA in gastric tumors was associated with the depth of the tumors, lymph-vascular invasion and lymph node involvement, suggesting that Il-17 obviously was related to tumor progression. Il-17 and Il-21, which regulates Il-17, would be potential therapeutic targets for the treatment of gastric cancer.

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Regulation of Gut Inflammation and Th17 Cell Response by Interleukin-21

Cited by 246 publications

References 24 publications

Signal Transducer and Activator of Transcription 3 - A Promising Target in Colitis-Associated Cancer

Signal Transducer and Activator of Transcription 3 - A Promising Target in Colitis-Associated Cancer

Interleukin-23 and T helper 17-type responses in intestinal inflammation: from cytokines to T-cell plasticity

Tumor-infiltrating CD4+ Th17 cells produce IL-17 in tumor microenvironment and promote tumor progression in human gastric cancer

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