Interleukin 13 and its role in gut defence and inflammation

Mannon, Peter J.; Reinisch, Walter

doi:10.1136/gutjnl-2012-303461

Cited by 97 publications

(84 citation statements)

References 108 publications

(73 reference statements)

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“…Additionally, IL-13 is proposed to play an important role in fistulizing CD. IL-13 expression is increased in transitional cells at the border of fistula tracks, where it induces expression of target genes involved in fistula formation (Mannon and Reinisch 2012). In our study we investigated cells isolated of whole blood samples, so that we could exclude any influence of IL-13 producing cells involved in fistulizing CD.…”

Section: Discussionmentioning

confidence: 99%

Cyclosporine A Regulates Pro-Inflammatory Cytokine Production in Ulcerative Colitis

Steiner

Daniel

Fischer

et al. 2014

Arch. Immunol. Ther. Exp.

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Crohn's disease (CD) and ulcerative colitis (UC) are the two major forms of inflammatory bowel diseases (IBD), which are defined as relapsing inflammations of the gastrointestinal tract. Cyclosporine A (CsA) is a potential rescue treatment to avoid colectomy in severe steroid-refractory UC patients. The molecular mechanism of action of CsA in UC is nevertheless still not well understood. The aim of this study was to investigate the effect of CsA on a possible modulation of cytokine production by peripheral blood mononuclear cells (PBMCs) of controls and patients with UC or CD. Upon CsA treatment, analyses of cytokine levels revealed a significant reduction of IL-13 expression in PBMCs from patients with UC, whereas other cytokine expression levels remained unaffected. To address the question whether CsA treatment impinges on the induction of cell death, apoptosis assays were performed using CD4? T cells from peripheral blood of patients suffering from either UC or CD. It became clear that CsA treatment resulted in a specific induction of apoptosis in samples from controls and patients with UC but not with CD. Apoptosis induction was not mediated via the mitochondrial apoptosis pathway. The present data support the concept that CsA treatment modulates proinflammatory cytokine production and T cell survival in UC via the induction of apoptosis and might therefore help to explain the clinical efficacy of CsA in patients with UC.

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Section: Discussionmentioning

confidence: 99%

Cyclosporine A Regulates Pro-Inflammatory Cytokine Production in Ulcerative Colitis

Steiner

Daniel

Fischer

et al. 2014

Arch. Immunol. Ther. Exp.

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“…QAX576, another fully human antibody against IL-13, is in phase I/II trials in patients with CD, the final results are pending [246,247].…”

Section: Inhibition Of Il-13mentioning

confidence: 99%

Gut Inflammation: Current Update on Pathophysiology, Molecular Mechanism and Pharmacological Treatment Modalities

Gyires¹,

Tóth²,

Zádori

2014

CPD

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Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory condition of the gastrointestinal tract. The two main forms of IBD are Crohn's disease and ulcerative colitis. According to the recent concept the disease is caused by a combination of factors, including genetics, immune dysregulation, barrier dysfunction and the change in microbial flora. Environmental factors, such as changes in diet, antibiotic use, smoking or improved domestic hygiene (e.g. eradication of intestinal helminths) probably contribute to the development and increased prevalence of IBD. Dysregulation of mucosal immunity in IBD causes an overproduction of inflammatory cytokines which resulted in uncontrolled intestinal inflammation. Based on extensive research over the last decade, besides the conventional therapy, there are several novel pathways and specific targets, on which focus new therapeutics. New therapeutics aim 1./ to correct genetic susceptibility by stimulating NOD2 expression, TLR3 signaling or inhibition of TLR4 pathway, 2./ to restore the immune dysregulation by inhibition of pro-inflammatory cytokines (TNF-, IL-6, IL-13, IL-17, IL-18, IL-21), Th1 polarisation (IL-2, IL-12, IL-23, IFN-), T-cell activation, leukocyte adhesion, as well as by immunostimulation (GM-CSF, G-CSF) and anti-inflammatory cytokines (IL-10, IL-11, IFN--1a), 3./ to restore mucosal barrier function and stimulate mucosal healing by different growth factors, such as GH, EGF, KGF, TGF-, VEGF, 4./ to restore the normal bacterial flora by antibiotics, probiotics. However, in spite of these numerous potential targets, the true value and clinical significance of most of the new biologics and molecules are not clear yet.

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“…The present data and that of others support a role for IL-13 signaling in Teff alterations in T1D (48,49). Indeed, Teffs of patients with T1D expressed high levels of IL13Ra1 and low levels of IL13Ra2 compared with control subjects, and this can modulate IL-13 signaling in vivo (25,26). Albeit initially considered a decoy receptor, IL13Ra2-mediated signaling has been involved in the activation of the transforming growth factor-b1 (TGF-b1) promoter, underscoring its role as a signaling receptor (26).…”

Section: Discussionmentioning

confidence: 52%

“…Furthermore, IL13Ra2 receptor can act as a negative regulator of IL-13 effects. IL13Ra2, expressed after exposure to IL-13, exits rapidly to the cell membrane from intracellular locations to capture and internalize extracellular IL-13 (25). Because IL13Ra2 is a high-affinity receptor, this process reduces the IL-13 available to bind IL13Ra1 in a negative feedback loop.…”

Section: Discussionmentioning

confidence: 99%

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Interleukin-13 Pathway Alterations Impair Invariant Natural Killer T-Cell–Mediated Regulation of Effector T Cells in Type 1 Diabetes

et al. 2016

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Many studies have shown that human natural killer T (NKT) cells can promote immunity to pathogens, but their regulatory function is still being investigated. Invariant NKT (iNKT) cells have been shown to be effective in preventing type 1 diabetes in the NOD mouse model. Activation of plasmacytoid dendritic cells, modulation of B-cell responses, and immune deviation were proposed to be responsible for the suppressive effect of iNKT cells. We studied the regulatory capacity of human iNKT cells from control subjects and patients with type 1 diabetes (T1D) at disease clinical onset. We demonstrate that control iNKT cells suppress the proliferation of effector T cells (Teffs) through a cell contact–independent mechanism. Of note, suppression depended on the secretion of interleukin-13 (IL-13) by iNKT cells because an antibody blocking this cytokine resulted from the abrogation of Teff suppression; however, T1D-derived iNKT cells showed impaired regulation that could be attributed to the decrease in IL-13 secretion. Thus, alteration of the IL-13 pathway at disease onset may lead to the progression of the autoimmune response in T1D. Advances in the study of iNKT cells and the selection of agonists potentiating IL-13 secretion should permit new therapeutic strategies to prevent the development of T1D.

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Interleukin 13 and its role in gut defence and inflammation

Cited by 97 publications

References 108 publications

Cyclosporine A Regulates Pro-Inflammatory Cytokine Production in Ulcerative Colitis

Cyclosporine A Regulates Pro-Inflammatory Cytokine Production in Ulcerative Colitis

Gut Inflammation: Current Update on Pathophysiology, Molecular Mechanism and Pharmacological Treatment Modalities

Interleukin-13 Pathway Alterations Impair Invariant Natural Killer T-Cell–Mediated Regulation of Effector T Cells in Type 1 Diabetes

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