The Innate Immune System: A Trigger for Many Chronic Inflammatory Intestinal Diseases

Kamada, Nobuhiko; Rogler, Gerhard

doi:10.1159/000445261

Cited by 14 publications

(10 citation statements)

References 93 publications

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“…While the adaptive immune response plays a fundamental role in establishing a chronic inflammation, the innate immune machinery drives the initial steps of the inflammatory cascade (10). Production of innate pro-inflammatory cytokines, such as interleukin 15 (IL15) (11–13) and interferon alpha (IFNα) (14) has been reported in untreated CD patients upon ingestion of gliadin.…”

Section: Introductionmentioning

confidence: 99%

Intestinal Epithelium Modulates Macrophage Response to Gliadin in Celiac Disease

et al. 2019

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Celiac disease is an immune-mediated enteropathy triggered by ingestion of gluten. Although its pathogenesis has been extensively studied and the contribution from both innate and adaptive immune responses has been reported, little is still known about the contribution of macrophages to the onset or maintenance of the disease. Macrophages are extremely plastic immune cells that can be directed toward a pro- or anti-inflammatory phenotype by the surrounding microenvironment. Of note, gliadin, the most prominent causative agent of the disease, has been reported to trigger the production of pro-inflammatory cytokines in this cell population. In the present study, we aimed at investigating how the intestinal milieu and more specifically the epithelium can shape the macrophage response to gliadin. Using patient-derived organoids we showed that the intestinal epithelium derived from celiac disease donors releases anti-inflammatory factors that curb the macrophage response to gliadin. Furthermore, we uncovered that the celiac macrophages were better responders than macrophages derived from non-celiac controls. Finally, we demonstrated that IFNγ released by the epithelium is in part responsible of the observed anti-inflammatory effect. Our data shed light on the cross–talk between the immune system and the epithelium and its critical role in the intestinal homeostasis. Furthermore, we provide more evidence how alterations in the innate immune machinery in celiac patients may contribute to the onset of the disease.

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Section: Introductionmentioning

confidence: 99%

Intestinal Epithelium Modulates Macrophage Response to Gliadin in Celiac Disease

et al. 2019

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“…The inflammatory process underlying CD pathogenesis involves the activation of the innate as well as the adaptive immune system [26], being predominantly characterized by a strong T helper (Th)1 response with the production of pro-inflammatory cytokines, such as interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) [27]. The innate immune response is responsible for triggering the inflammatory cascade [28].…”

Section: Celiac Disease and Non-celiac Gluten Sensitivitymentioning

confidence: 99%

Brain Opioid Activity and Oxidative Injury: Different Molecular Scenarios Connecting Celiac Disease and Autistic Spectrum Disorder

et al. 2020

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Celiac Disease (CD) is an immune-mediated disease triggered by the ingestion of wheat gliadin and related prolamins from other cereals, such as barley and rye. Immunity against these cereal-derived proteins is mediated by pro-inflammatory cytokines produced by both innate and adaptive system response in individuals unable to adequately digest them. Peptides generated in this condition are absorbed across the gut barrier, which in these patients is characterized by the deregulation of its permeability. Here, we discuss a possible correlation between CD and Autistic Spectrum Disorder (ASD) pathogenesis. ASD can be induced by an excessive and inappropriate brain opioid activity during the neonatal period. Cereal-derived peptides produced in celiac patients cross the blood–brain barrier and bind to endogenous opioid receptors interfering with neurotransmission and generating deleterious effects on brain maturation, learning and social relations. Moreover, an increase in oxidative stress and a decrease in the antioxidant capacity, as well as an extended mitochondrial impairment in the brain, could represent a possible connection between ASD and CD. Therefore, we critically discuss the proposed relationship between ASD and CD and the possible usefulness of a gluten-free diet in ASD patients.

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“…In a recent review we highlighted the role of different macrophage populations in the intestinal mucosa 69 . Usually the differentiation of tissue macrophages in the mucosa is associated with a typical functional phenotype 63 : The majority of tissue macrophages found in IBD mucosa differs from the macrophages phenotype found in healthy mucosa 62,[70][71][72][73] .…”

Section: -The Role Macrophages In the Resolution Of Inflammation In Ibdmentioning

confidence: 99%

Resolution of inflammation in inflammatory bowel disease

Rogler

2017

The Lancet Gastroenterology & Hepatology

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Treatment of inflammatory bowel disease at present mainly targets mediators of inflammation to stop or suppress pro-inflammatory processes. Typical examples are steroids, suppression of T cells by thioguanine nucleotides, or antibodies against cytokines such as tumour necrosis factor, interleukin 12, or interleukin 23. In addition to suppression of inflammation, development of therapeutic strategies that support resolution of inflammation or that actively resolve inflammation might be desirable. Resolution of inflammation is now seen as an active process involving specific mediators (eg, lipid mediators or specific cytokines) that is mandatory to restore organ function and completely shut down inflammation. The molecular pathways involved in resolution of inflammation have been investigated in recent years and could be adopted in treatment strategies for inflammatory bowel disease. Among these approaches are anti-integrin strategies and means to produce or locally increase restitution or resolution factors, such as restoration of the activity of transforming growth factor-β by anti-SMAD7 antisense oligonucleotides. The potential role of inflammation-resolving lipid mediators (eg, resolvins), however, still warrants further study and clinical development. This Review focuses on the specific role of active resolution of inflammation in inflammatory bowel disease pathophysiology. Potential therapeutic targets based on these pathways are also discussed.

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The Innate Immune System: A Trigger for Many Chronic Inflammatory Intestinal Diseases

Cited by 14 publications

References 93 publications

Intestinal Epithelium Modulates Macrophage Response to Gliadin in Celiac Disease

Intestinal Epithelium Modulates Macrophage Response to Gliadin in Celiac Disease

Brain Opioid Activity and Oxidative Injury: Different Molecular Scenarios Connecting Celiac Disease and Autistic Spectrum Disorder

Resolution of inflammation in inflammatory bowel disease

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