IL24 — Interleukin 24

IL24 — Interleukin 24

<div class="infobox infobox-gene">

| Property | Value |
|----------|-------|
| Gene Symbol | IL24 |
| Full Name | Interleukin 24 |
| Chromosomal Location | 1q32.2 |
| NCBI Gene ID | 11009 |
| OMIM ID | 604136 |
| Ensembl ID | ENSG00000120289 |
| UniProt ID | Q13007 |
| Encoded Protein | Interleukin-24 (IL-24) |
| Associated Diseases | Alzheimer's disease, Parkinson's disease, cancer, inflammatory disorders |

</div>

Overview

IL24 (Interleukin-24) is a member of the IL-20 cytokine subfamily, which also includes IL-20, IL-22, and IL-26. Originally identified as a cytokine with tumor-suppressing properties, IL24 has emerged as a multifaceted cytokine with important functions in immune regulation, cell survival, and tissue homeostasis. Recent research has revealed that IL24 has significant roles in the central nervous system, where it modulates neuroinflammation, protects neurons from various insults, and may influence the progression of neurodegenerative diseases such as Alzheimer's and Parkinson's disease[@sau2003][@poirier2019].

IL24 — Interleukin 24

<div class="infobox infobox-gene">

| Property | Value |
|----------|-------|
| Gene Symbol | IL24 |
| Full Name | Interleukin 24 |
| Chromosomal Location | 1q32.2 |
| NCBI Gene ID | 11009 |
| OMIM ID | 604136 |
| Ensembl ID | ENSG00000120289 |
| UniProt ID | Q13007 |
| Encoded Protein | Interleukin-24 (IL-24) |
| Associated Diseases | Alzheimer's disease, Parkinson's disease, cancer, inflammatory disorders |

</div>

Overview

IL24 (Interleukin-24) is a member of the IL-20 cytokine subfamily, which also includes IL-20, IL-22, and IL-26. Originally identified as a cytokine with tumor-suppressing properties, IL24 has emerged as a multifaceted cytokine with important functions in immune regulation, cell survival, and tissue homeostasis. Recent research has revealed that IL24 has significant roles in the central nervous system, where it modulates neuroinflammation, protects neurons from various insults, and may influence the progression of neurodegenerative diseases such as Alzheimer's and Parkinson's disease[@sau2003][@poirier2019].

The IL24 gene encodes a secreted protein of approximately 206 amino acids that signals through a heterodimeric receptor complex composed of IL-20R1 and IL-20R2. Alternative signaling through IL-22R1/IL-20R2 has also been described. These receptors are expressed in various tissues including brain, where they are found on neurons, astrocytes, microglia, and oligodendrocytes. The widespread distribution of IL24 receptors in the CNS suggests diverse functions beyond the immune system[@wang2022].

Molecular Biology

Gene Structure

The IL24 gene is located on chromosome 1q32.2, a region that has been implicated in various autoimmune and inflammatory conditions. The gene consists of 5 exons spanning approximately 4.5 kb of genomic DNA. Several single nucleotide polymorphisms (SNPs) in the IL24 gene have been associated with:

• Cancer susceptibility
• Inflammatory disease risk
• Response to certain therapies

Protein Structure

IL24 is a secreted glycoprotein with the following features:

• Signal peptide: 23 amino acids at the N-terminus for secretion
• Core protein: 181 amino acids after signal peptide cleavage
• Glycosylation: Two N-linked glycosylation sites
• Molecular weight: Approximately 18-23 kDa depending on glycosylation state

Receptor Signaling

IL24 signals through two receptor complexes:

Type I receptor complex (IL-20R1/IL-20R2):

• High affinity binding for IL24
• Primarily expressed in skin, lung, and reproductive tissues
• Can also bind IL-20

• Lower affinity for IL24
• Expressed in many tissues including brain
• Also responds to IL-20 and IL-26

• JAK1/TYK2: Janus kinases associated with the receptor intracellular domains
• STAT3: Primary STAT transcription factor activated
• STAT1: Secondary STAT activation in some cell types
• MAPK pathway: ERK1/2 activation contributes to some biological effects

Functions in the Central Nervous System

Neuronal Expression and Effects

IL24 is expressed in various neuronal populations within the CNS:

• Hippocampal neurons: CA1-CA3 pyramidal neurons and dentate gyrus granule cells express IL24 receptors and respond to IL24 signaling
• Cortical neurons: Layer V pyramidal neurons show robust IL24R1 expression
• Cerebellar Purkinje cells: Express both IL24 and its receptors
• Substantia nigra dopaminergic neurons: Express IL24R1/IL20R2 receptor complex

Astrocyte Interactions

IL24 has important paracrine effects on astrocytes:

• Reactive astrogliosis: IL24 modulates astrocyte activation in response to CNS injury
• Inflammatory response: IL24 can both enhance and suppress astrocyte inflammatory cytokine production depending on context
• Neurotrophic support: Astrocyte-derived IL24 may support neuronal survival under stress

Microglial Regulation

Microglia, the resident immune cells of the brain, are major targets of IL24 action:

Anti-inflammatory effects: IL24 polarizes microglia toward an anti-inflammatory (M2-like) phenotype, characterized by:

• Increased IL-10 production
• Reduced TNF-α and IL-1β release
• Enhanced phagocytic activity

Spatial specificity: IL24 effects on microglia are spatially restricted, as the cytokine does not freely diffuse through tissue, allowing localized modulation of neuroinflammation[@khan2021][@liu2023].

Role in Alzheimer's Disease

Neuroinflammation Modulation

Alzheimer's disease is characterized by chronic neuroinflammation, with activated microglia and astrocytes contributing to both plaque clearance and neuronal damage. IL24 has emerged as a key modulator of this process:

Microglial activation: In AD models, IL24 treatment reduces microglial activation as measured by:

• Reduced Iba1 immunoreactivity
• Decreased CD68+ phagocytic microglia
• Lower expression of pro-inflammatory cytokines (IL-1β, TNF-α)

• Reduced GFAP upregulation
• Modified cytokine secretion profile
• Enhanced plaque-associated glial scar formation

Amyloid Metabolism

IL24 influences amyloid pathology through multiple mechanisms:

Tau Pathology

The effects of IL24 on tau pathology include:

• Phosphorylation modulation: IL24 can influence tau kinase/phosphatase balance
• Aggregation inhibition: Direct effects on tau aggregation have been reported
• Propagation: Effects on tau spread between neurons are under investigation

Cognitive Improvement

In mouse models of AD, IL24 administration (via viral vector or protein delivery) has been associated with:

• Improved spatial memory in Morris water maze
• Enhanced working memory in Y-maze
• Reduced anxiety-like behaviors
• Better performance in contextual fear conditioning

Role in Parkinson's Disease

Dopaminergic Neuron Protection

Parkinson's disease is characterized by progressive loss of dopaminergic neurons in the substantia nigra pars compacta. IL24 has shown protective effects in multiple PD models:

MPTP toxicity: In mice treated with the dopaminergic neurotoxin MPTP, IL24 treatment:

• Preserves tyrosine hydroxylase (TH)+ neurons
• Reduces caspase-3 activation in the substantia nigra
• Maintains striatal dopamine levels
• Improves behavioral performance

• Reduced α-synuclein aggregation
• Decreased neuronal loss
• Improved motor function

Neuroinflammation Suppression

Similar to its effects in AD, IL24 suppresses neuroinflammation in PD:

• Microglial activation: Reduced Iba1+ cell activation in substantia nigra
• Pro-inflammatory cytokines: Decreased TNF-α, IL-1β in the nigrostriatal system
• Anti-inflammatory cytokines: Increased IL-10 in the brain

Mechanisms of Protection

The neuroprotective effects of IL24 in PD involve:

• STAT3 activation: Critical for anti-apoptotic effects
• PI3K/Akt pathway: Contributes to cell survival signaling
• NF-κB inhibition: Suppresses inflammatory gene expression
• Mitochondrial protection: Preserves mitochondrial function under stress

Expression Patterns in the Brain

Cellular Distribution

| Cell Type | IL24 Expression | IL24R Expression |
|-----------|-----------------|------------------|
| Neurons (hippocampus) | Low | High |
| Neurons (cortex) | Low | Moderate-High |
| Dopaminergic neurons | Low | High |
| Astrocytes | Moderate | High |
| Microglia | Low (resting), High (activated) | Moderate |
| Oligodendrocytes | Low | Low-Moderate |

Regional Specificity

• Hippocampus: High IL24R expression in CA1-CA3 and dentate gyrus
• Cortex: Moderate-high expression in all layers
• Basal ganglia: High expression in substantia nigra and striatum
• Cerebellum: Moderate expression in Purkinje cell layer
• White matter: Low expression in oligodendrocytes

Regulation of IL24 Expression

Induced Expression

IL24 expression is induced by:

• Pro-inflammatory cytokines: IL-1β, TNF-α, IFN-γ
• Pattern recognition receptor activation: TLR ligands
• Cellular stress: DNA damage, oxidative stress
• Viral infection: Some viruses induce IL24

Transcriptional Control

• NF-κB: Primary transcription factor for IL24 induction
• AP-1: Cooperates with NF-κB for full activation
• STAT1: May contribute to IFN-γ-induced expression

Therapeutic Manipulation

Given its neuroprotective properties, IL24 is being explored as a therapeutic agent:

• Viral vector delivery: AAV-mediated IL24 expression
• Protein administration: Recombinant IL24 delivery
• Small molecule inducers: Compounds that boost endogenous IL24

Clinical Relevance

Biomarker Potential

IL24 levels in cerebrospinal fluid (CSF) may serve as:

• Disease progression marker in AD/PD
• Treatment response indicator
• Prognostic factor for cognitive decline

Therapeutic Development

IL24-based therapeutics face several challenges:

• Delivery: Crossing the blood-brain barrier
• Dosing: Defining therapeutic window
• Timing: Optimal intervention in disease course
• Safety: Potential off-target effects

Key Publications

See Also

• [Interleukins Overview](/mechanisms/interleukin-signaling) — IL family cytokines
• [Neuroinflammation](/mechanisms/neuroinflammation) — Inflammatory mechanisms in neurodegeneration
• [Alzheimer's Disease](/diseases/alzheimers-disease) — AD overview
• [Parkinson's Disease](/diseases/parkinsons-disease) — PD overview
• [Microglia](/cell-types/microglia) — Brain immune cells
• [JAK-STAT Signaling](/mechanisms/jak-stat-pathway) — IL24 signal transduction

External Links

• [NCBI Gene: IL24](https://www.ncbi.nlm.nih.gov/gene/11009)
• [Ensembl: ENSG00000120289](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000120289)
• [UniProt: Q13007](https://www.uniprot.org/uniprot/Q13007)
• [GeneCards: IL24](https://www.genecards.org/cgi-bin/carddisp.pl?gene=IL24)
• [OMIM: 604136](https://omim.org/entry/604136)

References