IL17A — Interleukin 17A

IL17A — Interleukin 17A

<div class="infobox infobox-gene">
<table>
<tr><th colspan="2" style="background:#f0f0f0;">IL17A</th></tr>
<tr><td><b>Full Name</b></td><td>Interleukin 17A</td></tr>
<tr><td><b>Symbol</b></td><td>IL17A</td></tr>
<tr><td><b>Chromosome</b></td><td>6p12.2</td></tr>
<tr><td><b>NCBI Gene ID</b></td><td>[3605](https://www.ncbi.nlm.nih.gov/gene/3605)</td></tr>
<tr><td><b>Ensembl ID</b></td><td>ENSG00000112116</td></tr>
<tr><td><b>OMIM ID</b></td><td>603250</td></tr>
<tr><td><b>UniProt ID</b></td><td>[Q16552](https://www.uniprot.org/uniprot/Q16552)</td></tr>
<tr><td><b>Protein Size</b></td><td>155 amino acids (homodimer)</td></tr>
<tr><td><b>Associated Diseases</b></td><td>[Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), [Multiple Sclerosis](/diseases/multiple-sclerosis), Stroke</td></tr>
</table>
</div>

Overview

IL17A — Interleukin 17A

<div class="infobox infobox-gene">
<table>
<tr><th colspan="2" style="background:#f0f0f0;">IL17A</th></tr>
<tr><td><b>Full Name</b></td><td>Interleukin 17A</td></tr>
<tr><td><b>Symbol</b></td><td>IL17A</td></tr>
<tr><td><b>Chromosome</b></td><td>6p12.2</td></tr>
<tr><td><b>NCBI Gene ID</b></td><td>[3605](https://www.ncbi.nlm.nih.gov/gene/3605)</td></tr>
<tr><td><b>Ensembl ID</b></td><td>ENSG00000112116</td></tr>
<tr><td><b>OMIM ID</b></td><td>603250</td></tr>
<tr><td><b>UniProt ID</b></td><td>[Q16552](https://www.uniprot.org/uniprot/Q16552)</td></tr>
<tr><td><b>Protein Size</b></td><td>155 amino acids (homodimer)</td></tr>
<tr><td><b>Associated Diseases</b></td><td>[Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), [Multiple Sclerosis](/diseases/multiple-sclerosis), Stroke</td></tr>
</table>
</div>

Overview

IL17A (Interleukin-17A) is the founding member of the IL-17 cytokine family, encoded by the IL17A gene on chromosome 6p12.2. It is a 155-amino acid secreted glycoprotein that forms disulfide-linked homodimers. IL-17A is produced primarily by Th17 cells (a distinct CD4+ T helper subset), as well as by innate immune cells including gamma-delta (γδ) T cells, innate lymphoid cells type 3 (ILC3s), natural killer T (NKT) cells, and neutrophils. IL-17A is a potent pro-inflammatory cytokine that plays critical roles in host defense against extracellular bacteria and fungi, but is also central to the pathogenesis of autoimmune diseases and has been increasingly recognized as a contributor to neuroinflammation in neurodegenerative diseases [@kolls2012][@linares2013].

Molecular Function

Receptor and Signaling

IL-17A signals through a heterodimeric receptor complex:

• IL17RA (IL-17 Receptor A): ubiquitously expressed, forms the signaling subunit
• IL17RC: co-receptor, especially highly expressed in non-immune cells including neurons and glia

• NF-κB pathway: Classical pro-inflammatory signaling via IKK complex activation
• MAPK pathways: C/EBPβ, C/EBPδ, and AP-1 family transcription factors
• C/EBP activation: Gene expression programs for chemokines and inflammatory mediators

| Target Type | Examples | Function |
|------------|----------|----------|
| Pro-inflammatory cytokines | IL-6, TNF-α, IL-1β | Amplify inflammation |
| Chemokines | CXCL1, CXCL8, CCL20 | Recruit neutrophils |
| Antimicrobial peptides | β-defensins, S100A8/A9 | Host defense |
| MMPs | MMP1, MMP3, MMP9 | Tissue remodeling |

Cellular Sources

• Th17 cells: CD4+ T helper cells differentiated under TGF-β, IL-6, IL-21, and IL-23
• γδ T cells: Innate-like T cells producing IL-17A rapidly in response to stress
• ILC3s: Innate lymphoid cells providing early IL-17A response
• Neutrophils: Can produce IL-17A in chronic inflammatory settings

Role in Neurodegeneration

Alzheimer's Disease

IL-17A levels are elevated in the [cerebrospinal fluid](/entities/cerebrospinal-fluid) and brain tissue of [Alzheimer's Disease](/diseases/alzheimers-disease) patients. Key contributions include:

• Neuroinflammation amplification: IL-17A promotes chronic inflammation in the brain microenvironment, activating microglia and astrocytes
• [Blood-brain barrier](/entities/blood-brain-barrier) disruption: IL-17A increases BBB permeability, allowing peripheral immune cell infiltration
• Synapse toxicity: IL-17A signaling in neurons can lead to synaptic dysfunction and loss
• Aβ interaction: IL-17A may synergize with amyloid-β to drive microglial activation and neurotoxicity [@chai2023][@wu2017]

Parkinson's Disease

In [Parkinson's Disease](/diseases/parkinsons-disease), IL-17A contributes to dopaminergic neuron death through multiple mechanisms:

• Direct toxicity to dopaminergic neurons: IL-17A activates apoptotic pathways in [substantia nigra](/brain-regions/substantia-nigra) neurons
• Microglial activation: IL-17A is a potent activator of pro-inflammatory microglia (M1 phenotype)
• Th17 infiltration: Peripheral Th17 cells may cross the BBB and exacerbate nigral inflammation
• MPTP model evidence: In the MPTP mouse model of PD, IL-17A neutralization protects dopaminergic neurons and improves motor function [@yang2018][@yang2015]

Multiple Sclerosis

IL-17A is central to [Multiple Sclerosis](/diseases/multiple-sclerosis) pathogenesis:

• EAE induction: IL-17A is critical for experimental autoimmune encephalomyelitis (EAE), the mouse model of MS
• Demyelination: IL-17A drives oligodendrocyte death and myelin damage
• Clinical trials: Secukinumab (anti-IL-17A) showed efficacy in MS Phase II trials, with further studies ongoing [@bielekova2020]

Stroke and Ischemia

• Exacerbates ischemic injury: IL-17A levels rise rapidly after stroke and contribute to secondary neuronal damage
• Post-stroke inflammation: IL-17A from γδ T cells drives early inflammatory response that worsens outcomes

Therapeutic Targeting

Approved Biologicals

| Drug | Target | Indication | Notes |
|------|--------|------------|-------|
| Secukinumab | IL-17A | Psoriasis, Psoriatic Arthritis, Ankylosing Spondylitis | Approved; MS trials ongoing |
| Ixekizumab | IL-17A | Psoriasis, PsA | Approved |
| Bimekizumab | IL-17A/F | Psoriasis | Dual IL-17A/F inhibition |

Clinical Trials in Neurodegeneration

• Secukinumab in MS: Phase II trials showed reduced MRI lesions and clinical progression
• Rinvoq (JAK inhibitor): Indirectly reduces IL-17A signaling via JAK-STAT pathway; approved for inflammatory diseases

Challenges

• Infection risk: IL-17A blockade increases susceptibility to extracellular bacterial and fungal infections
• Mucosal immunity: Disruption of IL-17A-dependent host defense at barrier surfaces
• CNS delivery: Ensuring adequate CNS penetration for brain-resident inflammation

See Also

• [Neuroinflammation](/mechanisms/neuroinflammation) — Central role of IL-17A
• [Alzheimer's Disease](/diseases/alzheimers-disease) — AD neuroinflammation
• [Parkinson's Disease](/diseases/parkinsons-disease) — PD neuroinflammation
• [Multiple Sclerosis](/diseases/multiple-sclerosis) — MS autoimmune mechanisms
• [Th17 Cells](/entities/th17-cells) — IL-17A producing cells
• [Microglia](/cell-types/microglia) — Target cells in neuroinflammation
• [NF-κB Signaling](/entities/nf-kb) — Downstream pathway of IL-17A

Pathway Diagram

The following diagram shows the key molecular relationships involving il17a discovered through SciDEX knowledge graph analysis:

Pathway Diagram

The following diagram shows the key molecular relationships involving IL17A — Interleukin 17A discovered through SciDEX knowledge graph analysis: