IL17B (Interleukin 17B)
Overview
flowchart TD
IL17B["IL17B"] -->|"promotes"| Macrophage_Recruitment["Macrophage Recruitment"]
IL17B["IL17B"] -->|"binds"| IL17RB["IL17RB"]
Schwann_Cell["Schwann Cell"] -->|"expressed in"| IL17B["IL17B"]
style IL17B fill:#4fc3f7,stroke:#333,color:#000
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.
<div class="infobox infobox-gene">
...IL17B (Interleukin 17B)
Overview
Mermaid diagram (expand to render)
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.
<div class="infobox infobox-gene">
| 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 |
</div>
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-17RAReceptor 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 lossAmyotrophic Lateral Sclerosis
Motor Neuron Vulnerability: IL-17B affects motor neuron survival
Astrocyte Reactivity: Modulates reactive astrocyte responses
Microglial Activation: Creates inflammatory milieuOther 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 conditionsInteractions 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 therapeuticsClinical 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 riskDetection 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 |
See Also
- [Interleukin-17](/entities/interleukin-17)
- [Neuroinflammation](/mechanisms/neuroinflammation-mechanisms)
- [Th17 Cells](/entities/th17-cells)
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Parkinson's Disease](/diseases/parkinsons-disease)
- [Microglia in Neurodegeneration](/entities/microglia)
- [Cytokine Signaling in Brain](/mechanisms/cytokine-signaling)
- [IL-17 Family Cytokines](/mechanisms/il-17-family)
- [Neuroimmune Signaling](/entities/neuroimmune-signaling)
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/)