IL4 Gene

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IL4 Gene

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IL4 Gene

Introduction

Il4 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.

<table class="infobox infobox-gene"> [@gadani2012]
<tr><th colspan="2" style="background:#f0f0f0;">IL4</th></tr> [@lah2020]
<tr><td>Full Name</td><td>Interleukin 4</td></tr> [@woodling2019]
<tr><td>Chromosomal Location</td><td>5q31.3</td></tr> [@kummer2017]
<tr><td>NCBI Gene ID</td><td>[3560](https://www.ncbi.nlm.nih.gov/gene/3560)</td></tr>
<tr><td>OMIM</td><td>[147780](https://www.omim.org/entry/147780)</td></tr>
<tr><td>Ensembl ID</td><td>[ENSG00000100994](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000100994)</td></tr>
<tr><td>UniProt ID</td><td>[P05112](https://www.uniprot.org/uniprot/P05112)</td></tr>
<tr><td>Associated Diseases</td><td>Alzheimer's Disease, Parkinson's Disease, Asthma, Autoimmunity</td></tr>
</table>

Overview

...

IL4 Gene

Introduction

Il4 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)

IL4 is an anti-inflammatory cytokine that promotes microglial M2 polarization. It has neuroprotective properties and is being explored as a therapeutic target in neurodegenerative diseases.

Function

The IL4 gene encodes a protein involved in cellular signaling that is critical for development, tissue homeostasis, and immune regulation. In the nervous system, this protein plays important roles in neuroinflammation, neuronal survival, and synaptic plasticity.

Disease Associations

IL4 is associated with the following neurodegenerative and neurological conditions:

Alzheimer's Disease, Parkinson's Disease, Asthma, Autoimmunity

Expression

IL4 is expressed in various brain regions including [cortex](/brain-regions/cortex), [hippocampus](/brain-regions/hippocampus), and basal ganglia. The protein is produced by [neurons](/entities/neurons), [astrocytes](/entities/astrocytes), and [microglia](/entities/microglia), with expression levels varying in neurodegenerative conditions.

Key Publications

Wyss-Coray T, et al. (2000). TGF-beta1 and neurodegeneration. Nature. PMID: 11069107(https://pubmed.ncbi.nlm.nih.gov/11069107/).

Tesseur I, et al. (2006). Deficiency in neuronal TGF-beta signaling. Neuron. PMID: 16600861(https://pubmed.ncbi.nlm.nih.gov/16600861/).

Zhu Y, et al. (2004). IL-4 in neuroprotection. J Exp Med. PMID: 15467063(https://pubmed.ncbi.nlm.nih.gov/15467063/).

Butovsky O, et al. (2014). IL-4 and [microglia](/cell-types/microglia-neuroinflammation) polarization. Nat Neurosci. PMID: 24316888(https://pubmed.ncbi.nlm.nih.gov/24316888/).

Zhao X, et al. (2018). SMAD signaling in neurodegeneration. Cell Death Dis. PMID: 29348645(https://pubmed.ncbi.nlm.nih.gov/29348645/).

External Links

[NCBI Gene: IL4](https://www.ncbi.nlm.nih.gov/gene/3560)
[UniProt: IL4](https://www.uniprot.org/uniprot/P05112)
[Ensembl: IL4](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000100994)
[OMIM: IL4](https://www.omim.org/entry/147780)

Background

The study of Il4 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.

Molecular Biology

Cytokine Structure

IL4 is a 129-amino acid secreted cytokine with a characteristic four-helix bundle structure:

Molecular weight: ~15 kDa
Fold: Type I cytokine, four-helix bundle
Disulfide bonds: Two critical for stability
Receptor binding: Uses site I and site II interfaces

Receptor Complex

IL4 signals through two receptor complexes:

Type I receptor (lymphoid):

IL-4Rα (shared with IL-13)
Common γc chain (γc)
Signals primarily in lymphocytes

Type II receptor (type II):

IL-4Rα
IL-13Rα1
Used in non-immune cells including neurons

Signaling Pathways

IL4 activates multiple downstream pathways:

JAK-STAT6 pathway

JAK1/JAK3 phosphorylate STAT6
STAT6 dimerizes and translocates to nucleus
Drives M2 gene expression

PI3K-Akt pathway

Promotes cell survival
Anti-apoptotic effects
Important in neurons

MAPK pathway

ERK1/2 activation
Cell proliferation
Differentiation

Neuroprotective Mechanisms

Microglial Polarization

IL4 drives M2 (alternatively activated) microglial phenotype:

M2 markers:

Arg1 (Arginase 1)
Ym1 (chitinase-like 3)
Fizz1 (RELMα)
CD206 (mannose receptor)

Neuroprotective functions:

Anti-inflammatory: Produces IL-10, TGF-β
Trophic support: Secretes BDNF, IGF-1
Wound healing: Promotes tissue repair
[Aβ](/proteins/amyloid-beta) clearance: Enhanced phagocytosis

Direct Neuronal Effects

IL4 has direct effects on neurons:

Synaptic plasticity

Enhances [LTP](/mechanisms/long-term-potentiation) in hippocampus
Improves memory function
Modulates GABAergic signaling

Neuronal survival

Akt-mediated anti-[apoptosis](/entities/apoptosis)
Mitochondrial protection
Reduces excitotoxicity

Neurogenesis

Promotes hippocampal neurogenesis
Supports neural stem cells
Spatial memory improvement

Alzheimer's Disease

Role in AD Pathology

IL4 has complex interactions with AD:

Amyloid-β

Modulates Aβ production
Enhances microglial Aβ clearance
May reduce plaque burden

[Tau](/proteins/tau) pathology

Effects on [tau](/proteins/tau) phosphorylation
Modulates tau spreading
Neuroprotective against tau

Neuroinflammation

Shifts microglia to M2
Reduces pro-inflammatory cytokines
Improves cognitive function

Therapeutic Potential

IL4-based therapies for AD:

| Approach | Strategy | Status |
|----------|----------|--------|
| IL-4 delivery | Protein administration | Research |
| Gene therapy | AAV-IL4 | Preclinical |
| Small molecules | Enhance IL-4 signaling | Research |
| Peptide analogs | Modified IL-4 | Research |

Parkinson's Disease

Role in PD

IL4 is protective in PD models:

Dopaminergic neurons

Protects against MPTP toxicity
Reduces 6-OHDA damage
Promotes survival

Neuroinflammation

M2 microglial polarization
Reduced TNF-α, IL-1β
Enhanced dopamine function

[α-Synuclein](/proteins/alpha-synuclein)

Modulates aggregation
May enhance clearance
Neuroprotective

Clinical Evidence

Lower IL-4 in PD patients
Associated with disease progression
Genetic variants linked to risk

Amyotrophic Lateral Sclerosis

Role in ALS

IL4 has protective effects in ALS:

Neuroinflammation

M2 polarization beneficial
Reduces motor neuron death
Slows disease progression

Immune modulation

Regulatory T cell function
Anti-inflammatory environment

References

[@lah2020]

External Links

[NLRP6 Gene - NCBI](

Pathway Diagram

The following diagram shows the key molecular relationships involving IL4 Gene discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

📖 View canonical wiki page →

Related Entities

IL4

▸Metadataorigin_type: v1_polymorphic_backfill

slug	genes-il4
kg_node_id	IL4
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-2b49a276e62f
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-il4'}
_schema_version	1

📊 Evidence Profile Foundational

Evidence Balance

+0%

Certainty

65%

Debates

Incoming

Outgoing

0 supporting 0 contradicting 0 neutral

View full evidence profile →

🌍 Provenance Graph 1 nodes, 0 edges

No provenance edges found

This artifact has no version history yet.

Linked Artifacts (48)

see_also📖Amyloid-Related Imaging Abnormalities (ARIA)60%

see_also📖BMAL1 (ARNTL) Gene60%

see_also📖CAT — Catalase60%

see_also📖Alzheimer Indonesia60%

see_also📖APOE contributes to Alzheimer's disease by regulating b60%

see_also📖AMPK (AMP-Activated Protein Kinase)60%

see_also📖PRKCA — Protein Kinase C Alpha60%

see_also📖NPTX1 — Neuronal Pentraxin 160%

see_also📖CHIT1 Gene (Chitinase 1)60%

see_also📖Packard Center for ALS Research60%

see_also📖CHI3L1 Gene60%

see_also📖CD68 Gene60%

see_also📖CD200 Gene60%

see_also📖BDNF Gene60%

see_also📖ARRB2 — Arrestin Beta 260%

see_also📖Autophagy Enhancement Drug Screening for Neurodegeneration60%

see_also📖IL9 (Interleukin 9)60%

see_also📖ARRB1 — Arrestin Beta 160%

see_also📖CD200R1 Gene60%

see_also📖NPTX1 Protein60%

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mentions🧪Circadian Rhythm Entrainment of Reactive Astrocytes50%

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mentions🧪Cell-Type Specific TREM2 Upregulation in DAM Microglia50%

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mentions🧪Pericyte Contractility Reset via Selective PDGFR-β Agonism50%

mentions🧪APOE Isoform Expression Across Glial Subtypes50%

mentions🧪Temporal Decoupling via Circadian Clock Reset50%

mentions🧪GFAP-Positive Reactive Astrocyte Subtype Delineation50%

mentions🧪TREM2 Conformational Stabilizers for Synaptic Discrimination50%

mentions🧪Competitive APOE4 Domain Stabilization Peptides50%

mentions🧪Targeted APOE4-to-APOE3 Base Editing Therapy50%

mentions🧪APOE4 Allosteric Rescue via Small Molecule Chaperones50%

mentions🧪Astrocytic Lipoxin A4 Pathway Restoration via ALOX15 Gene Th50%

mentions🧪TREM2-mediated microglial tau clearance enhancement50%

mentions🧪Selective APOE4 Degradation via Proteolysis Targeting Chimer50%

mentions🔬Analyze circuit-level changes in neurodegeneration using All40%

Reference URLs

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📗 Cite This Artifact

IL4 Gene

IL4 Gene

Introduction

Overview

IL4 Gene

Introduction

Overview

Function

Disease Associations

Expression

Key Publications

See Also

External Links

Background

Molecular Biology

Cytokine Structure

Receptor Complex

Signaling Pathways

Neuroprotective Mechanisms

Microglial Polarization

Direct Neuronal Effects

Alzheimer's Disease

Role in AD Pathology

Therapeutic Potential

Parkinson's Disease

Role in PD

Clinical Evidence

Amyotrophic Lateral Sclerosis

Role in ALS

References

See Also

External Links

Pathway Diagram

💬 Discussion