Interleukin-13 Is the Key Effector Th2 Cytokine in Ulcerative Colitis That Affects Epithelial Tight Junctions, Apoptosis, and Cell Restitution

Heller, Frank; Florian, Peter; Bojarski, Christian; Richter, Jan F.; Christ, Melanie; Hillenbrand, Bernd; Mankertz, Joachim; Gitter, A. H.; Bürgel, Nataly; Fromm, Michael; Zeitz, Martin; Fuss, Ivan J.; Strober, Warren; Schulzke, Jörg D.

doi:10.1053/j.gastro.2005.05.002

Cited by 421 publications

(156 citation statements)

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“…A paradigm in IBD pathogenesis has been that UC is characterized by an atypical Th2 inflammation and CD by an inflammation where Th1 cytokines dominate (2,3). CXCL10 is considered as a chemokine that supports Th1-type inflammation and antagonizes Th2-type inflammation (18).…”

Section: Discussionmentioning

confidence: 99%

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Enhanced Expression of CXCL10 in Inflammatory Bowel Disease

Østvik

Granlund

Bugge

et al. 2013

Inflammatory Bowel Diseases

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We explored the gene expression in colonic biopsies of active and inactive inflammatory bowel disease (IBD), in an extensive material of ulcerative colitis (UC) and Crohn`s disease (CD). The chemokine CXCL10 and its receptor CXCR3 were among the upregulated genes.This study examines the expression of CXCL10 and the mechanisms for its release in patients with UC or CD, and in intestinal epithelial cell (IEC) lines. Methods

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Section: Discussionmentioning

confidence: 99%

“…Treg, has been of particular interest (2)(3)(4). One highly relevant chemokine in this context is CXCL10 (formerly IP-10: interferon-γ induced protein 10).…”

Section: Macrophages Dendritic Cells and Natural Killer T-cells) Andmentioning

confidence: 99%

Enhanced Expression of CXCL10 in Inflammatory Bowel Disease

Østvik

Granlund

Bugge

et al. 2013

Inflammatory Bowel Diseases

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“…Neither gender, nor age, nor extension of disease showed a significant effect on cytokine production (data not shown). IL-13, considered the effector cytokine in UC [2,3], was not differentially secreted between inflamed and noninflamed areas of gut of UC patients and in most cases (10 out of 11 from healthy and 6 out of 11 from inflamed areas) it was below detection limit so it did not correlate with severity of disease. IL-6 was the predominant cytokine found in inflamed areas of UC patients (2760 ± 813 pg/mL) (Fig.…”

Section: An Increased Pro-inflammatory Cytokine Profile In Inflamed Amentioning

confidence: 92%

“…Since IL-13 is considered to be the effector cytokine in UC [2,3] we performed blocking experiments in our culture system. Addition of anti-IL-13 to inflamed areas of UC patients did not decrease the secretion of the assayed cytokines.…”

Section: Il-6 Controls the Dysregulated Cytokine Profile In Uc Patientsmentioning

confidence: 99%

IL‐6 promotes immune responses in human ulcerative colitis and induces a skin‐homing phenotype in the dendritic cells and Tcells they stimulate

et al. 2012

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Dendritic cells (DCs) control the type and location of immune responses. Ulcerative colitis (UC) is considered a Th2 disease mediated by IL-13 where up to one third of patients can develop extraintestinal manifestations. Colonic biopsies from inflamed and noninflamed areas of UC patients were cultured in vitro and their supernatants were used to condition human blood enriched DCs from healthy controls. Levels of IL-13 in the culture supernatants were below the detection limit in most cases and the cytokine profile suggested a mixed profile rather than a Th2 cytokine profile. IL-6 was the predominant cytokine found in inflamed areas from UC patients and its concentration correlated with the Mayo endoscopic score for severity of disease. DCs conditioned with noninflamed culture supernatants acquired a regulatory phenotype with decreased stimulatory capacity. However, DCs conditioned with inflamed culture supernatants acquired a proinflammatory phenotype with increased expression of the skin-homing chemokine CCR8. These DCs did not have decreased T-cell stimulatory capacity and primed T cells with the skin-homing CLA molecule in an IL-6-dependent mechanism. Our results highlight the role of IL-6 in UC and question the concept of UC as a Th2 disease and the relevance of IL-13 in its etiology.Keywords: Dendritic cells r IL-6 r Mucosal immunity r Intestinal immunity r Ulcerative colitis Correspondence: Prof. Stella C. Knight e-mail: s.knight@imperial.ac.uk IntroductionThe gastrointestinal tract is in contact with a wide variety of commensal microbiota and diverse pathogens, and therefore C 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu 1338 David Bernardo et al. Eur. J. Immunol. 2012. 42: 1337-1353 requires a balance to be maintained between immunity and immune tolerance; the lack of immune responses against food antigens and/or the commensal microbiota is essential to maintain the homeostasis of the gastrointestinal tract [1]. Ulcerative colitis (UC) is a form of inflammatory bowel disease (IBD), traditionally related to a Th2 cytokine profile mediated by 3], where immune homeostasis of the gastrointestinal tract is compromised. Up to 1/3rd of UC patients can develop extraintestinal manifestations with the skin being one of such tissues [4,5].Dendritic cells (DCs) are the most potent antigen presenting cells and determine the nature and type of immune responses [6,7]. Intestinal DCs control immune tolerance in the gastrointestinal tract [8][9][10]. DCs also maintain immune responses localized to specific tissues, since they imprint specific tissue-homing profiles on stimulated T cells [11]. Retinoic acid (RA), the active form of vitamin A following dehydrogenization by the RALDH2 enzyme controls some of the mechanisms of immune homeostasis of the gut [12][13][14]. RA-producing DCs mediate the IgA switching of B cells [15], the generation of T cells with a regulatory phenotype [10], and the imprinting of gut-homing markers on B and T cells [16,17], thereby keeping tolerogenic immune responses com...

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“…While a primary barrier defect may be present in IBD kindreds 12-14 , it is also clear that epithelial barrier defects can be induced by inflammatory cytokines [15][16][17][18][19][20][21][22][23][24] . Recent work has demonstrated that barrier dysfunction induced by inflammatory processes can be due to epithelial damage as well as non-apoptotic regulation of tight junction permeability 19,22,[25][26][27][28] .…”

Section: Introductionmentioning

confidence: 99%

LIGHT Signals Directly to Intestinal Epithelia to Cause Barrier Dysfunction via Cytoskeletal and Endocytic Mechanisms

et al. 2007

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BACKGROUND & AIMS-LIGHT (lymphotoxin-like inducible protein that competes with glycoprotein D for herpes virus entry on T cells) is a TNF core family member that regulates T cell activation and causes experimental inflammatory bowel disease. Additional data suggest that LIGHT may be involved in the pathogenesis of human inflammatory bowel disease. The aim of this study was to determine if LIGHT was capable of signaling directly to intestinal epithelia and to define the mechanisms and consequences of such signaling.

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Interleukin-13 Is the Key Effector Th2 Cytokine in Ulcerative Colitis That Affects Epithelial Tight Junctions, Apoptosis, and Cell Restitution

Cited by 421 publications

References 40 publications

Enhanced Expression of CXCL10 in Inflammatory Bowel Disease

Enhanced Expression of CXCL10 in Inflammatory Bowel Disease

IL‐6 promotes immune responses in human ulcerative colitis and induces a skin‐homing phenotype in the dendritic cells and Tcells they stimulate

LIGHT Signals Directly to Intestinal Epithelia to Cause Barrier Dysfunction via Cytoskeletal and Endocytic Mechanisms

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