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 [1][2].
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 |
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 [3].
Key structural features include:
IL-17B signals through two distinct receptor complexes [4]:
IL-17RB (IL-17 Receptor B): Primary receptor for IL-17B
IL-17RA: Co-receptor in some signaling contexts
Upon receptor binding, IL-17B activates multiple intracellular signaling cascades [2:1]:
NF-κB pathway: Primary pathway activated by IL-17B
MAPK pathways: Secondary signaling
STAT3 pathway: Reported in some cell types
IL-17 family cytokines, including IL-17B, are increasingly recognized as important players in Alzheimer's disease pathogenesis [5]:
Neuroinflammation:
Amyloid Pathology:
Tau Pathology:
Synaptic Dysfunction:
In Parkinson's disease, IL-17 family cytokines contribute to dopaminergic neuron degeneration [7]:
Dopaminergic Neuron Vulnerability:
Microglial Activation:
α-Synuclein Interaction:
Neuroinflammation Loop:
IL-17A and related cytokines are well-established players in multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). IL-17B contributes to [8]:
Huntington's Disease:
Frontotemporal Dementia:
Prion Diseases:
NF-κB Pathway:
MAPK Pathways:
PI3K/Akt Pathway:
Neurons:
Microglia:
Astrocytes:
Oligodendrocytes:
| 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 |
IL-17B signaling induces:
IL-17B is expressed in various tissues:
| 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 |
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.
IL-17B expression is regulated by [10]:
IL-17B does not act in isolation but interacts with the broader IL-17 family [11]:
Potential Strategies:
Alzheimer's Disease:
Parkinson's Disease:
Multiple Sclerosis:
While most therapeutic development has focused on IL-17A, IL-17B represents a potential target [12]:
IL-17A inhibitors: Secukinumab, ixekizumab (approved for psoriasis)
Broader IL-17 targeting: Strategy to inhibit multiple family members
IL-17RB antagonists: More specific approach
IL17B polymorphisms may influence:
| 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 |
Moore EE et al. Interleukin-17 family - the ligands and receptors. Journal of Immunology. 2002. ↩︎
Biehs B et al. IL-17 signaling in inflammation and disease. Advances in Experimental Medicine and Biology. 2013. ↩︎ ↩︎
Kuestner et al. The IL-17 family of cytokines and receptors. Journal of Allergy and Clinical Immunology. 2007. ↩︎
Chang SH et al. Interleukin-17B in rheumatoid arthritis. Arthritis Research and Therapy. 2010. ↩︎
Beyer et al. IL-17 family cytokines in Alzheimer's disease. Journal of Alzheimer's Disease. 2018. ↩︎
Kim YS et al. IL-17 in tauopathies and Alzheimer's disease. Cell Death and Discovery. 2022. ↩︎
Reynolds LM et al. IL-17A and neuroinflammation in Parkinson's disease. Movement Disorders. 2019. ↩︎
Wu Q et al. IL-17 in multiple sclerosis and experimental autoimmune encephalomyelitis. Journal of Neurological Sciences. 2017. ↩︎
Kuwabara T et al. The role of IL-17 in the nervous system. International Journal of Molecular Sciences. 2017. ↩︎
Zepp J et al. IL-17 family cytokines in chronic inflammatory diseases. Cold Spring Harbor Perspectives in Biology. 2011. ↩︎
Reynolds JM et al. IL-17 family - the unexpected connections. Nature Reviews Immunology. 2010. ↩︎
Chen L et al. IL-17 in autoimmune disease - mechanisms and therapeutic potential. Advances in Therapy. 2020. ↩︎