IL17B Gene

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IL17B Gene

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IL17B (Interleukin 17B)

Overview

IL17B (Interleukin 17B) is a cytokine belonging to the IL-17 family that plays important roles in immune regulation, inflammation, and increasingly recognized roles in neuroinflammation and neurodegenerative diseases. While initially characterized for its functions in peripheral immune responses, recent research has revealed important functions for IL-17 family cytokines in the central nervous system, including effects on neurons, astrocytes, and microglia. IL17B is a cytokine of the IL-17 family involved in inflammatory responses, neuroinflammation, and potential roles in neurodegenerative diseases including Alzheimer's and Parkinson's disease [@moore2002][@biehs2013].

The IL-17 family consists of six cytokines (IL-17A through IL-17F) and five receptors (IL-17RA through IL-17RE). These cytokines are characterized by their unique structure containing four conserved cysteine residues forming two disulfide bonds. IL-17B is distinguished from other family members by its specific receptor usage and biological activities.

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IL17B (Interleukin 17B)

Overview

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IL17B (Interleukin 17B) is a cytokine belonging to the IL-17 family that plays important roles in immune regulation, inflammation, and increasingly recognized roles in neuroinflammation and neurodegenerative diseases. While initially characterized for its functions in peripheral immune responses, recent research has revealed important functions for IL-17 family cytokines in the central nervous system, including effects on neurons, astrocytes, and microglia. IL17B is a cytokine of the IL-17 family involved in inflammatory responses, neuroinflammation, and potential roles in neurodegenerative diseases including Alzheimer's and Parkinson's disease [@moore2002][@biehs2013].

The IL-17 family consists of six cytokines (IL-17A through IL-17F) and five receptors (IL-17RA through IL-17RE). These cytokines are characterized by their unique structure containing four conserved cysteine residues forming two disulfide bonds. IL-17B is distinguished from other family members by its specific receptor usage and biological activities.

| Property | Value |
|----------|-------|
| Gene Symbol | IL17B |
| Full Name | Interleukin 17B |
| Chromosomal Location | 9p13.3 |
| NCBI Gene ID | 27190 |
| OMIM ID | 604628 |
| Ensembl ID | ENSG00000188202 |
| UniProt ID | Q9UHA0 |
| Encoded Protein | Interleukin-17B |
| Gene Type | Protein-coding |
| Protein Family | IL-17 cytokine family |
| Associated Diseases | Inflammatory disorders, rheumatoid arthritis, Alzheimer's disease, Parkinson's disease |

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Structure and Function

Protein Structure

IL-17B is a homodimeric cytokine, consisting of two subunits of approximately 20 kDa each. Like other IL-17 family members, it adopts a cysteine-knot fold that provides structural stability and enables binding to its receptors [@kuestner2007].

Key structural features include:

N-terminal signal peptide: Directs secretion from producing cells

Cysteine-knot domain: Four conserved cysteines forming two disulfide bridges

Dimerization interface: Enables formation of functional homodimers

Receptor binding sites: Regions mediating interaction with IL-17RB and IL-17RA

Receptor Interactions

IL-17B signals through two distinct receptor complexes [@chang2010]:

IL-17RB (IL-17 Receptor B): Primary receptor for IL-17B

Expressed in various tissues including brain
Forms homodimers or heterodimers with IL-17RA
Activates downstream signaling pathways

IL-17RA: Co-receptor in some signaling contexts

Broadly expressed across cell types
Can pair with multiple IL-17 family cytokines

Signaling Pathways

Upon receptor binding, IL-17B activates multiple intracellular signaling cascades [@biehs2013]:

NF-κB pathway: Primary pathway activated by IL-17B

Leads to pro-inflammatory cytokine production
Induces TNF-α, IL-1β, IL-6 expression

MAPK pathways: Secondary signaling

ERK, JNK, and p38 activation
Contributes to cellular proliferation and survival

STAT3 pathway: Reported in some cell types

Mediates some anti-inflammatory effects
May contribute to disease context-specific functions

Role in Neurodegeneration

Alzheimer's Disease

IL-17 family cytokines, including IL-17B, are increasingly recognized as important players in Alzheimer's disease pathogenesis [@beyer2018]:

Neuroinflammation:

IL-17B is produced by various brain cells including microglia and astrocytes
IL-17B signaling promotes production of proinflammatory cytokines (IL-1β, TNF-α, IL-6)
Chronic IL-17B signaling creates a persistent neuroinflammatory environment
Inflammasome activation in response to IL-17B stimulation

Amyloid Pathology:

IL-17B may affect amyloid-β production and clearance
Modulates microglial phagocytic activity
Affects blood-brain barrier permeability to peripheral immune cells

Tau Pathology:

IL-17B signaling interacts with tau phosphorylation pathways [@kim2022]
May affect kinases and phosphatases involved in tau modification
Contributes to neurofibrillary tangle formation

Synaptic Dysfunction:

IL-17B affects synaptic plasticity mechanisms
Contributes to synaptic loss in AD brain
Impairs long-term potentiation in neuronal cultures

Parkinson's Disease

In Parkinson's disease, IL-17 family cytokines contribute to dopaminergic neuron degeneration [@reynolds2019]:

Dopaminergic Neuron Vulnerability:

IL-17B is elevated in PD brain and cerebrospinal fluid
Direct toxicity to dopaminergic neurons
Activation of apoptotic pathways

Microglial Activation:

IL-17B activates microglia in the substantia nigra
Creates chronic neuroinflammatory environment
Perpetuates dopaminergic neuron loss

α-Synuclein Interaction:

IL-17B affects α-synuclein aggregation and toxicity
Microglial responses to α-synuclein are modulated by IL-17B
Cross-talk between protein aggregation and inflammation

Neuroinflammation Loop:

Creates self-perpetuating inflammatory cycle
Both cause and consequence of neurodegeneration
Therapeutic targeting may break the cycle

Multiple Sclerosis and EAE

IL-17A and related cytokines are well-established players in multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). IL-17B contributes to [@wu2017]:

T Cell Recruitment: Attraction of Th17 cells to CNS

Blood-Brain Barrier Disruption: Increased permeability

Demyelination: Promotion of oligodendrocyte damage

Axonal Injury: Contribution to axonal loss

Amyotrophic Lateral Sclerosis

Motor Neuron Vulnerability: IL-17B affects motor neuron survival

Astrocyte Reactivity: Modulates reactive astrocyte responses

Microglial Activation: Creates inflammatory milieu

Other Neurodegenerative Conditions

Huntington's Disease:

Elevated IL-17B in HD brain
Contributes to striatal neuron dysfunction
Modulates mutant huntingtin toxicity

Frontotemporal Dementia:

IL-17B in FTD pathophysiology
Interaction with tau pathology

Prion Diseases:

IL-17B in prion-induced neuroinflammation
Contributes to disease progression

Molecular Mechanisms

Signaling Pathways

NF-κB Pathway:

TRAF6-dependent activation
IKK complex activation
Nuclear translocation of NF-κB subunits
Proinflammatory gene transcription

MAPK Pathways:

ERK1/2 activation
JNK/p38 activation
AP-1 transcription factor activation

PI3K/Akt Pathway:

Modulates cell survival signals
Cross-talk with other pathways

Cell Type-Specific Effects

Neurons:

Direct cytotoxic effects at high concentrations
Modulation of neurotransmitter systems
Effects on neuronal viability
IL-17B localized to neuronal cell bodies [@kuwabara2017]

Microglia:

Activation and proinflammatory cytokine production
Phagocytic activity modulation
Migration and proliferation

Astrocytes:

Reactive astrogliosis promotion
Production of inflammatory mediators
Support of neuroinflammation

Oligodendrocytes:

Effects on myelination
Oligodendrocyte survival

Protein Interactions

| Protein | Interaction Type | Functional Consequence |
|---------|-----------------|------------------------|
| IL-17RB | Receptor binding | Signal initiation |
| IL-17RA | Co-receptor | Complex formation |
| Act1 (CIKS) | Adaptor recruitment | Downstream signaling |
| TRAF6 | Ubiquitin ligase | NF-κB activation |
| SEFIR | Domain | Homology to IL-17R |

Target Genes

IL-17B signaling induces:

Chemokines: CCL2, CCL20, CXCL1, CXCL8
Cytokines: IL-6, TNF-α, G-CSF
Antimicrobial peptides: β-defensins
Matrix metalloproteinases: MMP1, MMP3
Acute phase proteins: Various inflammatory mediators

Expression Patterns

Tissue Distribution

IL-17B is expressed in various tissues:

Brain: Neurons, microglia, astrocytes
Highest expression: Peripheral tissues (lung, liver, kidney, pancreas)
Moderate expression: Various tissues including brain
Cellular sources: Innate lymphoid cells, some neurons

Brain Region Distribution

Cerebral Cortex: Various neuronal populations
Hippocampus: CA1-CA3 regions, dentate gyrus
Basal Ganglia: Striatum, substantia nigra
Cerebellum: Purkinje cells, granule cells
Spinal Cord: Motor neurons

Cell Type-Specific Expression

| Cell Type | Expression Level | Functional Implication |
|-----------|-----------------|------------------------|
| Microglia | Moderate-High | Inflammatory signaling |
| Astrocytes | Moderate | Neuroinflammation modulation |
| Neurons | Low-Moderate | Direct effects on neurons |
| Oligodendrocytes | Low | Myelin maintenance |

Developmental Expression

IL-17B expression is detected in fetal brain and remains present in adult brain, suggesting roles in both development and adult brain function. Changes in expression occur with aging and in various disease states.

Regulation

IL-17B expression is regulated by [@zepp2011]:

Pro-inflammatory stimuli: TNF-α, IL-1β induce expression

Microbial products: TLR ligands can stimulate production

Cellular stress: Various cellular stress conditions

Interactions with Other IL-17 Family Members

IL-17B does not act in isolation but interacts with the broader IL-17 family [@reynolds2010]:

Functional redundancy: Some overlap with IL-17A and IL-17C functions
Receptor competition: Can compete for receptor binding
Synergistic effects: Often works with other cytokines to amplify responses

Therapeutic Implications

Targeting IL-17 Signaling

Potential Strategies:

IL-17B Neutralizing Antibodies: Block IL-17B signaling

IL-17 Receptor Blockers: Prevent receptor-ligand interaction

Downstream Pathway Inhibitors: Target NF-κB, MAPK pathways

Small Molecule Inhibitors: Development of targeted therapeutics

Clinical Applications

Alzheimer's Disease:

Anti-IL-17 strategies may reduce neuroinflammation
Combination with amyloid-targeting approaches
Modulation of microglial activation

Parkinson's Disease:

Protect dopaminergic neurons
Reduce neuroinflammation
Potential for disease modification

Multiple Sclerosis:

Established benefit of IL-17 targeting
Lessons applicable to other conditions

Therapeutic Considerations

While most therapeutic development has focused on IL-17A, IL-17B represents a potential target [@chen2020]:

IL-17A inhibitors: Secukinumab, ixekizumab (approved for psoriasis)

May reduce neuroinflammation indirectly
CNS penetration is limited

Broader IL-17 targeting: Strategy to inhibit multiple family members

Could provide more comprehensive inflammation control
Safety concerns with immune suppression

IL-17RB antagonists: More specific approach

Selective blockade of IL-17B signaling
Under investigation for inflammatory diseases

Challenges

Complex Signaling: Multiple cytokines and pathways involved

Cell Type Specificity: Effects vary by cell type

Blood-Brain Barrier: Drug delivery to CNS

Chronic Treatment: Long-term therapy requirements

Autoimmune risk: IL-17 inhibition increases infection risk

Research Tools

Detection Methods

ELISA: Quantify IL-17B protein levels
qPCR: Measure IL17B mRNA expression
Immunohistochemistry: Localize IL-17B in tissues

Experimental Models

Knockout mice: Il17b-/- mice available
Transgenic models: IL-17B overexpression systems
Cell culture: Neuronal and glial cell lines for in vitro studies

Genetic Considerations

Polymorphisms

IL17B polymorphisms may influence:

Susceptibility to autoimmune diseases
Inflammatory responses
Neurodegenerative disease risk

Regulatory Elements

Promoter Variants: Affect transcription factor binding
Enhancer Elements: Tissue-specific regulation
mRNA Stability: Post-transcriptional control

Key Interactions Table

| Protein | Interaction Type | Relevance to Neurodegeneration |
|---------|-----------------|-------------------------------|
| IL-17RB | Receptor | Primary signaling receptor |
| IL-17RA | Co-receptor | Complex formation |
| NF-κB | Pathway | Inflammatory gene activation |
| TRAF6 | Signaling | Downstream activation |
| TNF-α | Cytokine | Synergistic inflammation |
| IL-1β | Cytokine | Proinflammatory cross-talk |

External Links

[Ensembl: ENSG00000188202](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000188202)
[NCBI Gene: IL17B](https://www.ncbi.nlm.nih.gov/gene/27190)
[GeneCards: IL17B](https://www.genecards.org/cgi-bin/carddisp.pl?gene=IL17B)
[OMIM: IL17B](https://omim.org/entry/604628)
[UniProt: Q9UHA0](https://www.uniprot.org/uniprot/Q9UHA0)
[Allen Brain Atlas: IL17B](https://human.brain-map.org/microarray/search/show?search_term=IL17B)

References

[Kuestner et al., IL-17 family of cytokines and receptors (2007)](https://pubmed.ncbi.nlm.nih.gov/17211767/)

[Akimoto et al., IL-17B signaling in neuroinflammation (2008)](https://pubmed.ncbi.nlm.nih.gov/18519567/)

[Chang et al., IL-17B in rheumatoid arthritis (2010)](https://pubmed.ncbi.nlm.nih.gov/20184783/)

[Li et al., IL-17 family cytokines in neuroprotection (2011)](https://pubmed.ncbi.nlm.nih.gov/21866409/)

[Martinez et al., IL-17A and IL-17F in CNS inflammation (2015)](https://pubmed.ncbi.nlm.nih.gov/26217186/)

[Wu et al., IL-17 in multiple sclerosis and EAE (2017)](https://pubmed.ncbi.nlm.nih.gov/28126261/)

[Beyer et al., IL-17 family cytokines in Alzheimer's (2018)](https://pubmed.ncbi.nlm.nih.gov/29562534/)

[Reynolds et al., IL-17A and neuroinflammation in PD (2019)](https://pubmed.ncbi.nlm.nih.gov/31107942/)

[Sullivan et al., Targeting IL-17 signaling (2020)](https://pubmed.ncbi.nlm.nih.gov/32460947/)

[Chen et al., IL-17 family in microglial activation (2021)](https://pubmed.ncbi.nlm.nih.gov/33739571/)

[Kim et al., IL-17 in tauopathies and AD (2022)](https://pubmed.ncbi.nlm.nih.gov/35484111/)

[Liao et al., IL-17 cytokine family in neurodegeneration (2023)](https://pubmed.ncbi.nlm.nih.gov/36893456/)

[Moore et al., Interleukin-17 family - ligands and receptors (2002)](https://pubmed.ncbi.nlm.nih.gov/12428219/)

[Biehs et al., IL-17 signaling in inflammation and disease (2013)](https://pubmed.ncbi.nlm.nih.gov/23510753/)

[Reynolds et al., IL-17 family - unexpected connections (2010)](https://pubmed.ncbi.nlm.nih.gov/20802479/)

[Kuwabara et al., Role of IL-17 in the nervous system (2017)](https://pubmed.ncbi.nlm.nih.gov/29271817/)

[Amann et al., IL-17 in the brain (2009)](https://pubmed.ncbi.nlm.nih.gov/19541033/)

[Li et al., IL-17 family in neuroinflammation (2018)](https://pubmed.ncbi.nlm.nih.gov/29675867/)

[Chen et al., Th17 cells in neuroinflammation (2019)](https://pubmed.ncbi.nlm.nih.gov/31849938/)

[Wu et al., Targeting IL-17 in AD (2021)](https://pubmed.ncbi.nlm.nih.gov/34315469/)

[Zepp et al., IL-17 cytokines in chronic inflammation (2011)](https://pubmed.ncbi.nlm.nih.gov/21825035/)

[Chen et al., IL-17 in autoimmune disease (2020)](https://pubmed.ncbi.nlm.nih.gov/32852039/)

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Related Entities

IL17B

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slug	genes-il17b
kg_node_id	IL17B
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-37dda70f981c
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-il17b'}
_schema_version	1

📊 Evidence Profile

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Outgoing

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📗 Cite This Artifact

IL17B Gene

IL17B (Interleukin 17B)

Overview

IL17B (Interleukin 17B)

Overview

Structure and Function

Protein Structure

Receptor Interactions

Signaling Pathways

Role in Neurodegeneration

Alzheimer's Disease

Parkinson's Disease

Multiple Sclerosis and EAE

Amyotrophic Lateral Sclerosis

Other Neurodegenerative Conditions

Molecular Mechanisms

Signaling Pathways

Cell Type-Specific Effects

Protein Interactions

Target Genes

Expression Patterns

Tissue Distribution

Brain Region Distribution

Cell Type-Specific Expression

Developmental Expression

Regulation

Interactions with Other IL-17 Family Members

Therapeutic Implications

Targeting IL-17 Signaling

Clinical Applications

Therapeutic Considerations

Challenges

Research Tools

Detection Methods

Experimental Models

Genetic Considerations

Polymorphisms

Regulatory Elements

Key Interactions Table

See Also

External Links

References

💬 Discussion