Selective downregulation of retinoic acid-inducible gene I within the intestinal epithelial compartment in crohnʼs disease

Funke, Benjamin; Lasitschka, Felix; Roth, Wilfried; Penzel, Roland; Meuer, Stefan; Saile, Maria; Gretz, Norbert; Sido, Bernd; Schirmacher, Peter; Autschbach, Frank

doi:10.1002/ibd.21572

Cited by 27 publications

(16 citation statements)

References 38 publications

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“…Contamination of the microdissected epithelial cells by immune cells from the lamina propria was possible, and could provide an alternative explanation for the presence of differentially expressed immune-related genes and pathways in the epithelial cell microarrays. Future gene expression profiling of the colon epithelium should include a comparison of microdissected lamina propria gene expression profiles for genes known to be predominantly expressed in each compartment to confirm the specificity of the cell fractions, although this would not completely rule out some degree of cross-contamination [58]. In addition, the relative contribution of the epithelium compared to the immune cell infiltrates could be studied by comparing the gene expression of epithelial cells with immune cell aggregates microdissected from the same inflamed colon sections.…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Changes in the Colon Epithelium Are Similar to Those of Intact Colon during Late Inflammation in Interleukin-10 Gene Deficient Mice

et al. 2013

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In addition to their role in absorption and secretion, epithelial cells play an important role in the protection of the colon mucosa from the resident microbiota and are important for the maintenance of homeostasis. Microarray analysis of intact colon samples is widely used to gain an overview of the cellular pathways and processes that are active in the colon during inflammation. Laser microdissection of colon epithelial cells allows a more targeted analysis of molecular pathways in the mucosa, preceding and during inflammation, with potentially increased sensitivity to changes in specific cell populations. The aim of this study was to investigate the molecular changes that occur in early and late inflammation stages in colon epithelium of a mouse model of inflammatory bowel diseases. Microarray analysis of intact colon samples and microdissected colon epithelial cell samples from interleukin-10 gene deficient and control mice at 6 and 12 weeks of age was undertaken. Results of gene set enrichment analysis showed that more immune-related pathways were identified between interleukin-10 gene deficient and control mice at 6 weeks of age in epithelial cells than intact colon. This suggests that targeting epithelial cells could increase sensitivity for detecting immune changes that occur early in the inflammatory process. However, in the later stages of inflammation, microarray analyses of intact colon and epithelium both provide a similar overview of gene expression changes in the colon mucosa at the pathway level.

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Section: Discussionmentioning

confidence: 99%

Gene Expression Changes in the Colon Epithelium Are Similar to Those of Intact Colon during Late Inflammation in Interleukin-10 Gene Deficient Mice

et al. 2013

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“…One report shows that subjects with Crohn's disease but not ulcerative colitis exhibit a selective suppression of RIG-I expression in the intestinal epithelial compartment (Funke, Lasitschka et al 2011). In another report, RIG-I-deficient mice generated by the deletion of exons 4-8 spontaneously develop a phenotype characteristic of autoimmune colitis.…”

Section: Rlr Polymorphisms and Immune Diseasementioning

confidence: 99%

Immune Signaling by RIG-I-like Receptors

2011

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The RIG-I-like receptors (RLRs) RIG-I, MDA5, and LGP2 play a major role in pathogen sensing of RNA virus infection to initiate and modulate antiviral immunity. The RLRs detect viral RNA ligands or processed self RNA in the cytoplasm to triggers innate immunity and inflammation and to impart gene expression that serves to control infection. Importantly, RLRs cooperate in signaling crosstalk networks with Toll-like receptors and other factors to impart innate immunity and to modulate the adaptive immune response. RLR regulation occurs at a variety of levels ranging from autoregulation to ligand and co-factor interactions and post-translational modifications. Abberant RLR signaling or dysregulation of RLR expression is now implicated in the development of autoimmune diseases. Understanding the processes of RLR signaling and response will provide insights to guide RLR-targeted therapeutics for antiviral and immune modifying applications.

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“…Mice lacking RIG-I have fewer and smaller Peyer’s patches, as well as an increase in apoptotic B220+ cells within the patches [47]. Additionally, CD patients have decreased levels of RIG-I in the intestinal epithelium [48]. In a healthy individual, the interferon response is negatively regulated via autophagy through the association with RIG-I and MAVS [49] or with NOD2 [50], and the development of autoimmunity is avoided.…”

Section: Rna Sensing Dysfunction and Autoimmunitymentioning

confidence: 99%

Nucleic Acid Sensing and Innate Immunity: Signaling Pathways Controlling Viral Pathogenesis and Autoimmunity

Ahlers

Goodman

2016

Curr Clin Micro Rpt

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Innate immunity refers to the body’s initial response to curb infection upon exposure to invading organisms. While the detection of pathogen-associated molecules is an ancient form of host defense, if dysfunctional, autoimmune disease may result. The innate immune response during pathogenic infection is initiated through the activation of receptors recognizing conserved molecular patterns, such as nucleic acids from a virus’ genome or replicative cycle. Additionally, the host’s own nucleic acids are capable of activating an immune response. Therefore, it follows that the nucleic acid-sensing pathways must be tightly controlled to avoid an autoimmune response from recognition of self, yet still be unimpeded to respond to viral infections. In this review, we will describe the nucleic acid sensing pathways and how they respond to virus infection. Moreover, we will discuss autoimmune diseases that develop when these pathways fail to signal properly and identify knowledge gaps that are prime for interrogation.

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Selective downregulation of retinoic acid-inducible gene I within the intestinal epithelial compartment in crohnʼs disease

Abstract: Epithelial downregulation of RIG-I, a known pattern recognition receptor for viral components, might contribute to alterations of the innate mucosal immune response, particularly in CD.

Cited by 27 publications

References 38 publications

Gene Expression Changes in the Colon Epithelium Are Similar to Those of Intact Colon during Late Inflammation in Interleukin-10 Gene Deficient Mice

Gene Expression Changes in the Colon Epithelium Are Similar to Those of Intact Colon during Late Inflammation in Interleukin-10 Gene Deficient Mice

Immune Signaling by RIG-I-like Receptors

Nucleic Acid Sensing and Innate Immunity: Signaling Pathways Controlling Viral Pathogenesis and Autoimmunity

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