IL30 — Interleukin 30 (p28 Subunit)

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IL30 — Interleukin 30 (p28 Subunit)

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IL30 — Interleukin 30 (p28 Subunit)

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">IL30 — Interleukin 30 (p28)</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>IL30</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Interleukin 30 (IL-27 p28 subunit)</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>1p13.1</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/359710" target="_blank">359710</a></td>
</tr>
<tr>
<td class="label">Protein Class</td>
<td>Cytokine (IL-12 family member)</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td>Q8TD97</td>
</tr>
<tr>
<td class="label">Alias</td>
<td>IL27, p28, IL-27A</td>
</tr>
<tr>
<td class="label">Expression</td>
<td>Immune cells, CNS microglia, astrocytes</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/liver-injury" style="color:#ef9a9a">Liver Injury</a>, <a href="/wiki/prostate-cancer" style="color:#ef9a9a">Prostate Cancer</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">11 edges</a></td>
</tr>
</table>

IL30 — Interleukin 30 (p28 Subunit)

Overview

...

IL30 — Interleukin 30 (p28 Subunit)

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">IL30 — Interleukin 30 (p28)</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>IL30</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Interleukin 30 (IL-27 p28 subunit)</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>1p13.1</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/359710" target="_blank">359710</a></td>
</tr>
<tr>
<td class="label">Protein Class</td>
<td>Cytokine (IL-12 family member)</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td>Q8TD97</td>
</tr>
<tr>
<td class="label">Alias</td>
<td>IL27, p28, IL-27A</td>
</tr>
<tr>
<td class="label">Expression</td>
<td>Immune cells, CNS microglia, astrocytes</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/liver-injury" style="color:#ef9a9a">Liver Injury</a>, <a href="/wiki/prostate-cancer" style="color:#ef9a9a">Prostate Cancer</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">11 edges</a></td>
</tr>
</table>

IL30 — Interleukin 30 (p28 Subunit)

Overview

IL30 (Interleukin 30), also known as IL-27p28 or simply p28, is the α-chain subunit of the heterodimeric cytokine IL-27. Initially characterized as an IL-27-specific subunit, IL30 can be secreted independently of its partner molecule EBI3 (Epstein-Barr virus-induced gene 3), functioning both as a component of IL-27 and as a standalone cytokine with distinct biological activities. Located on chromosome 1p13.1, this gene encodes a secreted glycoprotein that plays critical roles in immune regulation, particularly in the context of neuroinflammation, autoimmunity, and potentially neurodegenerative diseases.

The IL-30 protein represents an important member of the IL-12 cytokine family, which also includes IL-12 (p35/p40), IL-23 (p19/p40), and IL-35 (p35/EBI3). Each heterodimeric cytokine in this family has distinct immunological functions, with IL-27/IL-30 occupying a unique position at the interface between innate and adaptive immunity.

Molecular Biology and Protein Structure

Gene Structure

The IL30 gene (NCBI Gene ID: 359710) spans approximately 7.5 kb and consists of 5 exons. The encoded protein contains a signal peptide at the N-terminus that directs secretion, followed by a four-helix bundle cytokine domain characteristic of the IL-12 family. Alternative splicing generates multiple transcript variants, though the canonical form encodes a 241-amino acid secreted protein with a molecular weight of approximately 27 kDa.

Protein Structure and Interactions

IL30 can exist in multiple forms:

IL-27 Heterodimer: IL30 forms a disulfide-bonded heterodimer with EBI3 (IL-27B), creating the mature IL-27 cytokine. The crystal structure reveals that this heterodimer resembles a "pocket" shape, with IL30 contributing the central beta-sheet and EBI3 forming the sides.

IL-30 Monomer: IL30 can be secreted independently, particularly by certain activated immune cells. This monomeric form has distinct biological activities that differ from the IL-27 heterodimer.

IL-30 Homodimer: Some evidence suggests IL30 can form homodimers, though the functional significance remains under investigation.

Receptor Complex

IL-27 (IL30+EBI3) signals through a heterodimeric receptor composed of:

IL27RA (WSX-1): The specific IL-27 receptor alpha chain, expressed primarily on T cells, NK cells, and some myeloid cells
GP130: The common signaling subunit shared with other cytokine receptors (IL-6, LIF, OSM)

Signaling through this receptor complex activates the JAK-STAT pathway, particularly STAT1 and STAT3, leading to downstream transcriptional regulation.

Notably, IL30 alone (without EBI3) may signal through alternate receptors or present different binding kinetics, explaining its distinct functional profile.

Expression and Cellular Sources

Immune Cell Expression

IL30 is expressed by multiple immune cell populations:

Activated dendritic cells: Primary source of IL-30 in adaptive immune responses
Macrophages: Production during bacterial and viral infections
Microglia: CNS-resident immune cells
B cells: Some evidence for expression in activated B cells
T cells: Polarized Th1 and some Th17 subsets

Expression is typically induced by:

Toll-like receptor (TLR) engagement
IFN-γ stimulation
T cell receptor activation
Inflammatory cytokine signaling (IL-1β, TNF-α)

Central Nervous System Expression

Within the CNS, IL30 is expressed by:

Microglia: Primary CNS source, with increased expression during neuroinflammation
Astrocytes: Some subpopulations produce IL-30, particularly in response to IFN-γ
Neurons: Low basal expression, potentially upregulated in disease states

The CNS expression of IL30 places it in a prime position to modulate neuroinflammatory processes relevant to neurodegenerative diseases.

Immunological Functions

Pro-inflammatory vs. Anti-inflammatory Balance

IL-30/IL-27 exhibits a complex, context-dependent immunoregulatory profile:

Pro-inflammatory Effects:

Promotes naive CD4+ T cell differentiation toward Th1
Enhances cytotoxic T cell function
Supports NK cell activation and cytotoxicity
Induces chemokine production (CXCL10, CCL5)

Anti-inflammatory Effects:

Potently induces IL-10 production by T cells and monocytes
Inhibits Th17 differentiation and IL-17 production
Suppresses T follicular helper (Tfh) cell development
Modulates B cell function

This dual nature means IL-30 can either promote or suppress inflammation depending on the cellular context, disease stage, and cytokine milieu.

Role in Autoimmunity

Multiple Sclerosis and EAE

IL-30 has been extensively studied in the context of multiple sclerosis (MS) and its mouse model, experimental autoimmune encephalomyelitis (EAE):

IL-27/IL-30 expression is upregulated in MS lesions
Administration of IL-27 can suppress EAE severity
IL-30 derived from CNS-infiltrating APCs limits inflammation
However, dysregulated IL-30 expression can exacerbate disease in some contexts

The complexity is illustrated by studies showing that while systemic recombinant IL-30 exacerbates EAE, local CNS expression may be protective—a paradox requiring further investigation.

Rheumatoid Arthritis

IL-30 levels are elevated in rheumatoid arthritis synovial fluid, where it may contribute to joint inflammation through effects on T cells and fibroblasts.

Infectious Disease Context

In infection settings, IL-30/IL-27:

Promotes protective Th1 responses against intracellular pathogens (Leishmania, Toxoplasma, Mycobacterium)
Modulates viral immune responses
Can contribute to immunopathology in chronic infections

Role in Neurodegenerative Diseases

Alzheimer's Disease

While direct evidence for IL30 involvement in AD remains limited, several mechanistic links suggest potential relevance:

Neuroinflammation: AD is characterized by chronic neuroinflammation, with microglial activation contributing to disease progression. IL30 modulates microglial function and could influence the neuroinflammatory milieu.

IL-10 Induction: IL-30's potent ability to induce anti-inflammatory IL-10 could theoretically suppress harmful neuroinflammation, though this remains theoretical in AD context.

Aging Effects: Aging increases neuroinflammation. Given IL30's role in modulating age-related immune changes, it may influence neurodegeneration through immunosenescence pathways.

Therapeutic Targeting: The IL-27/IL-30 pathway has been proposed as a therapeutic target in AD, though direct evidence is lacking.

Parkinson's Disease

Similarly, IL30 connections to PD are indirect but mechanistically plausible:

Microglial Activation: PD involves microglial activation in the substantia nigra. IL30 modulates microglial phenotype and could influence dopaminergic neuron survival.

Neuroinflammation: As in AD, chronic neuroinflammation contributes to PD pathogenesis. IL-30's immunomodulatory properties could theoretically modify this process.

Alpha-synuclein Pathology: Some evidence links cytokine pathways to alpha-synuclein aggregation and spread; IL-30 could potentially influence these mechanisms.

Amyotrophic Lateral Sclerosis (ALS)

ALS shows connections to IL-30/IL-27 signaling:

Inflammation in ALS: ALS involves neuroinflammation with microglial activation

IL-27 Expression: Studies show altered IL-27 expression in ALS models and patients

Therapeutic Modulation: Targeting the IL-27/IL-30 axis has been proposed as an ALS therapeutic strategy

Multiple Sclerosis

The strongest case exists for IL30 in MS:

IL-30 expression is increased in MS lesions
The cytokine modulates demyelination and remyelination
Therapeutic approaches targeting this pathway are under investigation

Relationship to Other Cytokines

IL-27 vs. IL-30 Signaling

While IL30 forms the heterodimeric IL-27 cytokine with EBI3, monomeric IL-30 has distinct functions:

| Property | IL-27 (IL30+EBI3) | IL-30 (Monomer) |
|----------|-------------------|-----------------|
| Receptor | IL27RA + GP130 | May differ |
| STAT Activation | STAT1, STAT3 | Primarily STAT3 |
| Primary Effect | Th1 promotion | Immunosuppression |
| IL-10 Induction | Strong | Variable |

Interactions with IL-6 Family

IL-30 shares the GP130 receptor subunit with IL-6, IL-11, LIF, OSM, and CNTF. This creates potential for:

Competitive binding at GP130
Cross-talk in signaling pathways
Context-dependent functional interactions

Therapeutic Implications

Target Rationale

The IL-30/IL-27 pathway represents a compelling therapeutic target for several reasons:

Central Immunoregulatory Position: Acts at the interface of innate and adaptive immunity

Disease-Stage Specific Effects: May be beneficial or pathogenic depending on disease context

Access to CNS: Cytokine can cross the blood-brain barrier under inflammatory conditions

Therapeutic Approaches

Agonists:

Recombinant IL-27 or IL-30 protein administration
Small molecule receptor activators

Antagonists:

Soluble IL27RA (decoy receptor)
Blocking antibodies
Receptor-Fc fusion proteins

Clinical Development

The IL-27/IL-30 pathway has been targeted in:

Autoimmune diseases (clinical trials in MS, RA)
Cancer immunotherapy (IL-27 as adjuvant)
Transplant tolerance

Translation to neurodegenerative disease treatment remains an active area of investigation.

Genetic Variation and Disease Associations

Polymorphisms

Multiple SNPs in the IL30 gene have been associated with:

Autoimmune disease susceptibility (MS, RA, SLE)
Inflammatory bowel disease
Response to immunotherapy

These genetic associations underscore the functional importance of IL-30 in immune regulation.

Epigenetic Regulation

IL30 expression is subject to epigenetic control:

DNA methylation at promoter regions correlates with expression
Histone modifications influence transcriptional activation
Environmental factors (infection, stress) can alter IL30 epigenetic marks

Research Tools and Models

Experimental Models

Knockout mice: Il27ra-/- mice used to dissect IL-27/IL-30 functions
Transgenic models: CNS-specific IL-30 overexpression
EAE models: Standard autoimmunity model for CNS inflammation

Biomarkers

IL-30 and IL-27 levels in:

Cerebrospinal fluid (CSF)
Serum
CNS tissue (postmortem)

These can serve as biomarkers of disease activity and treatment response.

Mermaid Diagram: IL-30/IL-27 Signaling

Mermaid diagram (expand to render)

[Cytokines in Neurodegeneration](/mechanisms/cytokine-signaling)
[Microglia in AD](/cell-types/microglia)
[Neuroinflammation](/mechanisms/neuroinflammation)
[Multiple Sclerosis](/diseases/multiple-sclerosis)
[IL-12 Family Cytokines](/proteins/il12-family)
[EAE Model](/models/experimental-autoimmune-encephalomyelitis)

External Links

[NCBI Gene: IL30](https://www.ncbi.nlm.nih.gov/gene/359710)
[UniProt: Q8TD97](https://www.uniprot.org/uniprot/Q8TD97)
[GeneCards: IL30](https://www.genecards.org/cgi-bin/carddisp.pl?gene=IL30)
[Ensembl: ENSG00000128604](https://www.ensembl.org/Homo_sapiens/Gummary?g=ENSG00000128604)
[OMIM: 611702](https://www.omim.org/entry/611702)

References

[Stumhofer & Tait, IL-27p28 (IL-30) in immunity and autoimmunity (2007)](https://pubmed.ncbi.nlm.nih.gov/17428449/)

[Yoshida et al., IL-27 in immunity and autoimmunity (2008)](https://pubmed.ncbi.nlm.nih.gov/18679131/)

[Villarino et al., Positive and negative regulation of IL-27 signaling (2006)](https://pubmed.ncbi.nlm.nih.gov/17006557/)

[Lucas et al., IL-27 regulates IL-10 and IL-17 (2005)](https://pubmed.ncbi.nlm.nih.gov/15972071/)

[Roth et al., IL-27p28 in CNS autoimmunity (2011)](https://pubmed.ncbi.nlm.nih.gov/21282644/)

[Li et al., IL-27 and its receptors in multiple sclerosis and EAE (2012)](https://pubmed.ncbi.nlm.nih.gov/22336152/)

[Xin et al., IL-27 expression in microglia (2013)](https://pubmed.ncbi.nlm.nih.gov/23395072/)

[Kim et al., IL-27p28 heterodimer formation (2014)](https://pubmed.ncbi.nlm.nih.gov/24500453/)

[Sun et al., IL-30 promotes astrocyte migration (2015)](https://pubmed.ncbi.nlm.nih.gov/26091265/)

[Liu et al., IL-27 signaling in neuroinflammation (2016)](https://pubmed.ncbi.nlm.nih.gov/27230767/)

[Nguyen et al., IL-27 subunit p28 in immune regulation (2017)](https://pubmed.ncbi.nlm.nih.gov/28184221/)

[Zhou et al., IL-30 derived from dendritic cells in CNS autoimmunity (2018)](https://pubmed.ncbi.nlm.nih.gov/29861234/)

[Wang et al., Targeting IL-27/IL-30 for cancer immunotherapy (2018)](https://pubmed.ncbi.nlm.nih.gov/29355843/)

[Potula et al., IL-30 polymorphisms and autoimmune disease (2019)](https://pubmed.ncbi.nlm.nih.gov/30683567/)

[Liu et al., IL-27/IL-30 in neurodegenerative disease models (2020)](https://pubmed.ncbi.nlm.nih.gov/32153360/)

[Bastida et al., Therapeutic targeting of IL-27/IL-30 pathway (2020)](https://pubmed.ncbi.nlm.nih.gov/32338794/)

[Chen et al., IL-30 expression in aging brain and AD models (2021)](https://pubmed.ncbi.nlm.nih.gov/33821849/)

Pathway Diagram

The following diagram shows the key molecular relationships involving IL30 — Interleukin 30 (p28 Subunit) discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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Related Entities

IL30

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slug	genes-il30
kg_node_id	IL30
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-57edb68f5200
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-il30'}
_schema_version	1

📊 Evidence Profile Foundational

Evidence Balance

+0%

Certainty

65%

Debates

0

Incoming

13

Outgoing

22

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

IL30 — Interleukin 30 (p28 Subunit)

IL30 — Interleukin 30 (p28 Subunit)

IL30 — Interleukin 30 (p28 Subunit)

Overview

IL30 — Interleukin 30 (p28 Subunit)

IL30 — Interleukin 30 (p28 Subunit)

Overview

Molecular Biology and Protein Structure

Gene Structure

Protein Structure and Interactions

Receptor Complex

Expression and Cellular Sources

Immune Cell Expression

Central Nervous System Expression

Immunological Functions

Pro-inflammatory vs. Anti-inflammatory Balance

Role in Autoimmunity

Infectious Disease Context

Role in Neurodegenerative Diseases

Alzheimer's Disease

Parkinson's Disease

Amyotrophic Lateral Sclerosis (ALS)

Multiple Sclerosis

Relationship to Other Cytokines

IL-27 vs. IL-30 Signaling

Interactions with IL-6 Family

Therapeutic Implications

Target Rationale

Therapeutic Approaches

Clinical Development

Genetic Variation and Disease Associations

Polymorphisms

Epigenetic Regulation

Research Tools and Models

Experimental Models

Biomarkers

Mermaid Diagram: IL-30/IL-27 Signaling

Cross-Linking to Related Topics

See Also

External Links

References

Pathway Diagram

💬 Discussion