IL-33 and the intestine: The good, the bad, and the inflammatory

Hodzic, Zerina; Schill, Ellen Merrick; Bolock, Alexa M.; Good, Misty

doi:10.1016/j.cyto.2017.06.017

Cited by 86 publications

(80 citation statements)

References 133 publications

(225 reference statements)

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“…Loss‐of‐function mutations in IL‐33 in allergic patients as well as in IL‐1R4 were identified, supporting the findings in genome‐wide association studies that identified the IL‐33/IL‐1R4 pathway as the most relevant factor in allergy . Besides allergic asthma, increased levels of IL‐33 have been found in many disorders associated with acute or chronic inflammation (reviewed in ) such as in the intestine (reviewed in ) and arthritis.…”

Section: Focus On the Il‐1r Familymentioning

confidence: 99%

The family of the interleukin‐1 receptors

Boraschi

Italiani

Weil

et al. 2017

Immunological Reviews

264

225

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The extracellular forms of the IL-1 cytokines are active through binding to specific receptors on the surface of target cells. IL-1 ligands bind to the extracellular portion of their ligand-binding receptor chain. For signaling to take place, a non-binding accessory chain is recruited into a heterotrimeric complex. The intracellular approximation of the Toll-IL-1-receptor (TIR) domains of the 2 receptor chains is the event that initiates signaling. The family of IL-1 receptors (IL-1R) includes 10 structurally related members, and the distantly related soluble protein IL-18BP that acts as inhibitor of the cytokine IL-18. Over the years the receptors of the IL-1 family have been known with many different names, with significant confusion. Thus, we will use here a recently proposed unifying nomenclature. The family includes several ligand-binding chains (IL-1R1, IL-1R2, IL-1R4, IL-1R5, and IL-1R6), 2 types of accessory chains (IL-1R3, IL-1R7), molecules that act as inhibitors of signaling (IL-1R2, IL-1R8, IL-18BP), and 2 orphan receptors (IL-1R9, IL-1R10). In this review, we will examine how the receptors of the IL-1 family regulate the inflammatory and anti-inflammatory functions of the IL-1 cytokines and are, more at large, involved in modulating defensive and pathological innate immunity and inflammation. Regulation of the IL-1/IL-1R system in the brain will be also described, as an example of the peculiarities of organ-specific modulation of inflammation.

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Section: Focus On the Il‐1r Familymentioning

confidence: 99%

The family of the interleukin‐1 receptors

Boraschi

Italiani

Weil

et al. 2017

Immunological Reviews

264

225

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“…Interleukin‐33 functions both as a cytokine and as a nuclear transcription factor . It activates both the innate and adaptive immune system and is a critical cytokine for Th2‐mediated host defense, as well as playing a key role in regulating immune responses in barrier tissues such as the intestine . Interleukin‐33 also functions as an alarmin and is released by epithelial and endothelial cells in response to cell injury and necrosis .…”

Section: Discussionmentioning

confidence: 99%

“…Also, because IL‐33 promotes an early Th2 immune response, it helps to regulate Th1 immune responses and prevent autoimmunity . Interleukin‐33 has been shown to influence both T regulatory cells and Th17 cells to decrease inflammation and protect the intestinal mucosa from self‐inflicted injury . Studies suggest that nuclear IL‐33 can sequester nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB), thereby decreasing subsequent NF‐κB‐generated proinflammatory signaling .…”

Section: Discussionmentioning

confidence: 99%

Interleukin‐13 and interleukin‐33 mRNA are underexpressed in the duodenal mucosa of German Shepherd dogs with chronic enteropathy

Kathrani

Lezcano

Hall

et al. 2019

Veterinary Internal Medicne

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Background A recent genome‐wide association study in German Shepherd dogs (GSDs) with chronic enteropathy (CE) has identified polymorphisms in the Th2 cytokine genes. Hypothesis/objective To determine if the expression of the Th2 cytokines, interleukin‐13 (IL‐13) and interleukin‐33 (IL‐33), is altered in the duodenal mucosa of GSDs with CE compared to non‐GSDs with CE and healthy dogs. Animals Twenty client‐owned dogs diagnosed with CE (10 GSDs and 10 non‐GSDs) at the Bristol Veterinary School and 8 healthy Beagle dogs from the Iowa State University Service Colony. Methods Retrospective study using archived paraffin‐embedded duodenal biopsy samples. A novel RNA in situ hybridization technology (RNAscope) was used to hybridize IL‐13 and IL‐33 mRNA probes onto at least 10 sections from duodenal biopsy samples for each dog. RNAscope signals were visualized using a microscope and semi‐quantitative assessment was performed by a single operator. Results Based on duodenal villus, subvillus, epithelial, and lamina propria average expression scores, GSDs with CE had significantly lower IL‐13 and IL‐33 mRNA expression compared to non‐GSDs with CE (IL‐13, P < .04; IL‐33, P < .02) and healthy Beagle dogs (IL‐13, P < .02; IL‐33, P < .004). Conclusions and Clinical Importance Similar to human patients with ulcerative colitis, a subtype of human inflammatory bowel disease, these data indicate that Th2 cytokines may be involved in the pathogenesis of CE in GSDs.

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“…The IL-33/ST2 axis is important for the maintenance of the epithelial integrity of the gastrointestinal tract [57]. Similar to its roles in the cardiovascular and central nervous system, IL-33 plays both beneficial and pathological roles in gastrointestinal diseases [57].…”

Section: Gastrointestinal Diseasesmentioning

confidence: 99%

“…Similar to its roles in the cardiovascular and central nervous system, IL-33 plays both beneficial and pathological roles in gastrointestinal diseases [57]. In mouse models of experimental colitis induced by dextran sulphate sodium (DSS) or trinitrobenzene sulfonic acid (TNBS), deficiency of the IL33 or IL1RL1 genes leads to amelioration of the disease, compared to its outcome in wild-type control mice, and treatment with an ST2 blocking antibody ameliorates experimental colitis by enhancing mucosal healing in mice [58].…”

Section: Gastrointestinal Diseasesmentioning

confidence: 99%

Therapeutic Strategies for Targeting IL-33/ST2 Signalling for the Treatment of Inflammatory Diseases

Chen

Tsai

Yang

et al. 2018

Cell Physiol Biochem

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Interleukin (IL)-33, a member of the IL-1 family of cytokines, is involved in innate and adaptive immune responses via interaction with its receptor, ST2. Activation of ST2 signalling by IL-33 triggers pleiotropic immune functions in multiple ST2-expressing immune cells, including macrophages, neutrophils, eosinophils, basophils, mast cells, type 2 helper T cells, regulatory T cells, and group 2 innate lymphoid cells. IL-33-mediated effector functions contribute to the tissue inflammatory and reparative responses in various organs including lung, skin, kidney, central nerve system, cardiovascular system, and gastrointestinal system. Endogenous IL-33/ ST2 signaling exhibits diverse immune regulatory functions during progression of different diseases. IL-33 likely functions as a disease sensitizer and plays pathological roles in inflamed tissues in allergic disorders that involve hyperreactive immune responses in the context of skin and pulmonary allergy. However, IL-33 also mediates tissue-protective functions during the recovery phase following tissue injury in the central nerve system and gastrointestinal system. Modulation of the IL-33/ST2 axis, therefore, represents a promising strategy for treating immune disorders that involve dysregulation of the cytokine signalling. In the past two decades, therapeutic strategies blocking IL-33/ST2 have been extensively studied for the treatment of diseases in animal models. In this review, the current progress on the development of therapeutic biologics for targeting IL-33/ST2 signalling in inflammatory diseases is summarized.

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IL-33 and the intestine: The good, the bad, and the inflammatory

Cited by 86 publications

References 133 publications

The family of the interleukin‐1 receptors

The family of the interleukin‐1 receptors

Interleukin‐13 and interleukin‐33 mRNA are underexpressed in the duodenal mucosa of German Shepherd dogs with chronic enteropathy

Therapeutic Strategies for Targeting IL-33/ST2 Signalling for the Treatment of Inflammatory Diseases

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