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.
| Gene Information |
|---|
| Gene Symbol | IL33 |
| Full Name | Interleukin-33 |
| Chromosomal Location | 9p24.1 |
| NCBI Gene ID | 90865 |
| OMIM | 608678 |
| Ensembl ID | ENSG00000144233 |
| UniProt | Q9BY84 |
| Associated Diseases | Alzheimer Disease, Parkinson Disease, Multiple Sclerosis, Asthma, Autoimmune Disorders |
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.
IL33 is a cytokine with alarmin function:
- N-terminal domain: Chromatin-binding domain
- C-terminal domain: Cytokine receptor-binding domain
- Full-length form: Biologically active as nuclear protein
- ST2/IL-1RAcP receptor: Activates MyD88 and NF-kB
- Soluble ST2: Decoy receptor that neutralizes IL-33
- Alternative splicing: Produces different isoforms
- Alarmin release: Released from damaged cells
- Type 2 immune responses: Promotes Th2 cytokine production
- Tissue homeostasis: Maintains stromal cells
- Association: IL33 expression altered in AD brain
- Mechanism: Modulates microglial activation and neuroinflammation
- Pathology: IL33+ cells near amyloid plaques
- Association: IL33 in PD pathogenesis
- Mechanism: Neuroinflammation and dopaminergic neuron survival
- Association: IL33 polymorphisms linked to MS risk
- Mechanism: Role in demyelination and neuroinflammation
| Cell Type |
Expression |
Notes |
| Astrocytes |
High |
Brain expression |
| Neurons |
Moderate |
Some neuronal types |
| Microglia |
Moderate |
Immune cells |
| Endothelial Cells |
High |
Vascular cells |
| Fibroblasts |
High |
Stromal cells |
| Strategy |
Approach |
Status |
| ST2 Antagonists |
Soluble ST2-Fc |
Research |
| Anti-IL33 |
Monoclonal antibodies |
Research |
| Natural Compounds |
Modulate IL-33 pathway |
Preclinical |
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 exerts multiple effects in the central nervous system:
- 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 activity
- Reactive astrocytes: IL-33 promotes astrocyte reactivity in neurodegeneration
- Blood-brain barrier: Affects BBB integrity and permeability
- Neuronal support: Provides trophic support to neurons
- Anti-apoptotic effects: Protects neurons from various stressors
- Synaptic plasticity: Influences synaptic formation and function
- Neurogenesis: Supports hippocampal neurogenesis
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
- Cognitive function: IL-33 treatment improves cognitive deficits in mouse models
In Parkinson's disease:
- Dopaminergic neurons: IL-33 protects dopaminergic neurons
- Neuroinflammation: Reduces neuroinflammatory responses
- Alpha-synuclein: Modulates α-synuclein pathology
- Mitochondrial function: Preserves mitochondrial integrity
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
- CSF levels: IL-33 in cerebrospinal fluid as a biomarker
- Blood-brain barrier penetration: Studies on therapeutic delivery
- Diagnostic utility: Potential for early diagnosis
- Recombinant IL-33: Protein replacement therapy
- ST2 agonists: Activating the IL-33 pathway
- Small molecules: Targeting the IL-33/ST2 axis
- 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
- Liew FY, Girard JP, Turnquist HR. Interleukin-33 in health and disease. Nat Rev Immunol. 2016;16(11):676-689
- 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
- Chapman J, Ng WYS, Nicoll JAR. The role of interleukin-33 in neurodegenerative diseases. J Neuroinflammation. 2022
- Fu AKY, Ip FCF, Ip NY. IL-33: a neuroprotective cytokine in Alzheimer's disease. J Alzheimers Dis. 2020
- Carlock C, Wu J, Zhou C, et al. IL-33 and ST2 as predictors of disease severity in coronavirus infection. Nat Commun. 2021