IL33 Gene

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IL33 - Interleukin-33

Introduction

Il33 Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

<div class="infobox .infobox-gene"> [@xiong2014]
<table> [@chapman2022]
<tr><th colspan="2" style="background:#f0f0f0;">Gene Information</th></tr> [@aky2020]
<tr><td><strong>Gene Symbol</strong></td><td>IL33</td></tr> [@carlock2021]
<tr><td><strong>Full Name</strong></td><td>Interleukin-33</td></tr>
<tr><td><strong>Chromosomal Location</strong></td><td>9p24.1</td></tr>
<tr><td><strong>NCBI Gene ID</strong></td><td>90865</td></tr>
<tr><td><strong>OMIM</strong></td><td>608678</td></tr>
<tr><td><strong>Ensembl ID</strong></td><td>ENSG00000144233</td></tr>
<tr><td><strong>UniProt</strong></td><td>Q9BY84</td></tr>
<tr><td><strong>Associated Diseases</strong></td><td>Alzheimer Disease, Parkinson Disease, Multiple Sclerosis, Asthma, Autoimmune Disorders</td></tr>
</table>
</div>

Overview

...

IL33 - Interleukin-33

Introduction

Il33 Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

Mermaid diagram (expand to render)

IL33 encodes Interleukin-33, a cytokine belonging to the IL-1 family that functions as an alarmin released upon cell damage. IL33 signals through the ST2 receptor (IL1RL1) and plays dual roles in both promoting and resolving inflammation. Recent research implicates IL33 in the pathogenesis of neurodegenerative diseases through its effects on neuroinflammation, glial cell function, and neuronal survival.

Normal Function

IL33 is a cytokine with alarmin function:

Protein Structure

N-terminal domain: Chromatin-binding domain
C-terminal domain: Cytokine receptor-binding domain
Full-length form: Biologically active as nuclear protein

Signaling Pathways

ST2/IL-1RAcP receptor: Activates MyD88 and [NF-kB](/entities/nf-kb)

Soluble ST2: Decoy receptor that neutralizes IL-33

Alternative splicing: Produces different isoforms

Molecular Functions

Alarmin release: Released from damaged cells
Type 2 immune responses: Promotes Th2 cytokine production
Tissue homeostasis: Maintains stromal cells

Disease Associations

Alzheimer Disease

Association: IL33 expression altered in AD brain
Mechanism: Modulates microglial activation and neuroinflammation
Pathology: IL33+ cells near amyloid plaques

Parkinson Disease

Association: IL33 in PD pathogenesis
Mechanism: Neuroinflammation and dopaminergic neuron survival

Multiple Sclerosis

Association: IL33 polymorphisms linked to MS risk
Mechanism: Role in demyelination and neuroinflammation

Expression Pattern

| Cell Type | Expression | Notes |
|----------|-----------|-------|
| [Astrocytes](/entities/astrocytes) | High | Brain expression |
| [Neurons](/entities/neurons) | Moderate | Some neuronal types |
| [Microglia](/cell-types/microglia-neuroinflammation) | Moderate | Immune cells |
| Endothelial Cells | High | Vascular cells |
| Fibroblasts | High | Stromal cells |

Therapeutic Targeting

| Strategy | Approach | Status |
|----------|----------|--------|
| ST2 Antagonists | Soluble ST2-Fc | Research |
| Anti-IL33 | Monoclonal antibodies | Research |
| Natural Compounds | Modulate IL-33 pathway | Preclinical |

Background

The study of Il33 Gene has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

IL-33 in Neurodegeneration

Mechanisms of Action

IL-33 exerts multiple effects in the central nervous system:

Neuroinflammation Modulation

Microglial activation: IL-33 polarizes microglia toward an anti-inflammatory (M2) phenotype
Cytokine regulation: Modulates production of IL-1β, TNF-α, and IL-6
Inflammasome inhibition: Reduces [NLRP3 inflammasome](/entities/nlrp3-inflammasome) activity

Astrocyte Function

Reactive astrocytes: IL-33 promotes astrocyte reactivity in neurodegeneration
[Blood-brain barrier](/entities/blood-brain-barrier): Affects BBB integrity and permeability
Neuronal support: Provides trophic support to neurons

Neuronal Survival

Anti-apoptotic effects: Protects neurons from various stressors
Synaptic plasticity: Influences synaptic formation and function
Neurogenesis: Supports hippocampal neurogenesis

Alzheimer Disease

The role of IL-33 in Alzheimer's disease has been extensively studied:

Amyloid pathology: IL-33 expression is reduced in AD brains
Plaque association: IL-33 accumulates around amyloid plaques
Microglial regulation: Modulates microglial phagocytosis of [Aβ](/proteins/amyloid-beta)
Cognitive function: IL-33 treatment improves cognitive deficits in mouse models

Parkinson Disease

In Parkinson's disease:

Dopaminergic neurons: IL-33 protects dopaminergic neurons
Neuroinflammation: Reduces neuroinflammatory responses
[Alpha-synuclein](/proteins/alpha-synuclein): Modulates α-synuclein pathology
Mitochondrial function: Preserves mitochondrial integrity

Amyotrophic Lateral Sclerosis

Emerging evidence for IL-33 in ALS:

Motor neuron protection: May protect motor neurons
Glial involvement: Modulates astrocyte and microglia function
Disease progression: Correlates with disease severity

Research Directions

Biomarker Potential

CSF levels: IL-33 in cerebrospinal fluid as a biomarker
Blood-brain barrier penetration: Studies on therapeutic delivery
Diagnostic utility: Potential for early diagnosis

Therapeutic Approaches

Recombinant IL-33: Protein replacement therapy
ST2 agonists: Activating the IL-33 pathway
Small molecules: Targeting the IL-33/ST2 axis

Key Publications

IL-33 in AD: Xiong et al. (2014) demonstrated altered IL-33 expression in AD brain

IL-33 mechanism: Liew et al. (2016) reviewed IL-33 signaling

Therapeutic potential: IL-33 treatment in mouse models of neurodegeneration

External Links

[NCBI Gene: IL33](https://www.ncbi.nlm.nih.gov/gene/90865)
[UniProt: IL33](https://www.uniprot.org/uniprot/Q9BY84)
[OMIM: IL33](https://www.omim.org/entry/608678)

References

[Unknown, Liew FY, Girard JP, Turnquist HR. Interleukin-33 in health and disease. Nat Rev Immunol. 2016;16(11):676-689 (2016)](https://doi.org/10.1038/nri.2016.95)

[Xiong Z, Thangavel R, Kempuraj D, et al., Alzheimer disease: evidence for the altered expression of IL-33 and its receptor ST2. J Alzheimers Dis. 2014;42(4):1271-1280 (2014)](https://doi.org/10.3233/JAD-140539)

[Unknown, Chapman J, Ng WYS, Nicoll JAR. The role of interleukin-33 in neurodegenerative diseases. J Neuroinflammation. 2022 (2022)](https://doi.org/10.1186/s12974-022-02452-8)

[Unknown, Fu AKY, Ip FCF, Ip NY. IL-33: a neuroprotective cytokine in Alzheimer's disease. J Alzheimers Dis. 2020 (2020)](https://doi.org/10.3233/JAD-190950)

[Carlock C, Wu J, Zhou C, et al., IL-33 and ST2 as predictors of disease severity in coronavirus infection. Nat Commun. 2021 (2021)](https://doi.org/10.1038/s41467-021-22118-w)

Pathway Diagram

The following diagram shows the key molecular relationships involving IL33 Gene discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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IL33 Gene

IL33 - Interleukin-33

Introduction

Overview

IL33 - Interleukin-33

Introduction

Overview

Normal Function

Protein Structure

Signaling Pathways

Molecular Functions

Disease Associations

Alzheimer Disease

Parkinson Disease

Multiple Sclerosis

Expression Pattern

Therapeutic Targeting

Background

IL-33 in Neurodegeneration

Mechanisms of Action

Neuroinflammation Modulation

Astrocyte Function

Neuronal Survival

Alzheimer Disease

Parkinson Disease

Amyotrophic Lateral Sclerosis

Research Directions

Biomarker Potential

Therapeutic Approaches

Key Publications

See Also

External Links

References

Pathway Diagram