IL22

IL22

Overview

```mermaid
flowchart TD
classDef gene fill:#0a1f0a,stroke:#4caf50
classDef protein fill:#0a1929,stroke:#2196f3
classDef disease fill:#2d0f0f,stroke:#e91e63
classDef pathway fill:#3e2200,stroke:#ff9800
classDef mechanism fill:#1a0a1f,stroke:#9c27b0
classDef therapeutic fill:#e0f2f1,stroke:#009688
IL22["IL22"] -->|"implicated_in"| neurodegeneration["neurodegeneration"]
IL22["IL22"] -->|"expressed_in"| GENES["GENES"]
IL22["IL22"] -->|"expressed_in"| IL31["IL31"]
IL22["IL22"] -->|"expressed_in"| S100A9["S100A9"]
IL22["IL22"] -->|"expressed_in"| Als["Als"]
IL22["IL22"] -->|"expressed_in"| Atherosclerosis["Atherosclerosis"]
IL22["IL22"] -->|"expressed_in"| Inflammation["Inflammation"]
IL22["IL22"] -->|"expressed_in"| Differentiation["Differentiation"]
IL22["IL22"] -->|"causes"| JAK["JAK"]
IL22["IL22"] ==>|"activates"| CD4["CD4"]
IL22["IL22"] -->|"causes"| Als["Als"]
IL22["IL22"] ==>|"activates"| Inflammation["Inflammation"]
IL22["IL22"] -->|"expressed_in"| RNA["RNA"]
IL22["IL22"] -->|"expressed_in"| IL4R["IL4R"]
IL22["IL22"] -->|"expressed_in"| IL_13["IL-13"]
IL22["IL22"] -->|"expressed_in"| CLDN1["CLDN1"]
IL22["IL22"] -->|"expressed_in"| S100A8["S100A8"]
IL22["IL22"] -->|"associated_with"| IL6R["IL6R"]
IL22["IL22"] -->|"associated_with"| MMP12["MMP12"]
IL22["IL22"] -->|"therapeutic_target"| Macrophage["Macrophage"]
IL22["IL22"] -->|"therapeutic_target"| T_Cell["T Cell"]
IL22["IL22"] -->|"expressed_in"| AND["AND"]
IL22["IL22"] -->|"expressed_in"|

IL22

Overview

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">IL22</th>
</tr>
<tr>
<td class="label">gene = IL22</td>
<td>name = Interleukin 22</td>
</tr>
<tr>
<td class="label">ncbi_gene_id = 50616</td>
<td>ensembl = ENSG00000127353</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/atherosclerosis" style="color:#ef9a9a">Atherosclerosis</a>, <a href="/wiki/inflammation" style="color:#ef9a9a">Inflammation</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">19 edges</a></td>
</tr>
</table>

IL22

{{ infobox .infobox-gene
| gene = IL22
| name = Interleukin 22
| chromosome = 12q13
| ncbi_gene_id = 50616
| ensembl = ENSG00000127353
| uniprot = Q9GZT6
| diseases = Inflammatory Disease, Psoriasis, Neuroinflammation
}}

Introduction

IL22 (Interleukin 22) is a member of the IL-10 cytokine family, encoded by the IL22 gene located on chromosome 12q13 [1](https://www.ncbi.nlm.nih.gov/gene/50616). IL22 is produced primarily by activated Th22 cells, Th17 cells, NK cells, and innate lymphoid cells [2](https://pubmed.ncbi.nlm.nih.gov/19237716/). Unlike other IL-10 family cytokines, IL22 signals through a distinct receptor complex (IL22R1/IL10R2) and exerts tissue-protective effects rather than primarily immunosuppressive functions [3](https://pubmed.ncbi.nlm.nih.gov/18836519/).

IL22 binds to IL22R1 (also known as IL22RA1), which is expressed mainly on epithelial cells and some stromal cells, but not on immune cells [4](https://pubmed.ncbi.nlm.nih.gov/19544425/). This unique receptor expression pattern means IL22 acts primarily on non-hematopoietic cells, promoting tissue repair, antimicrobial defense, and inflammation resolution.

The role of IL22 in neuroinflammation has become increasingly recognized, with implications for multiple sclerosis, autoimmune encephalitis, and other neurological conditions [5](https://pubmed.ncbi.nlm.nih.gov/32844137/).

Receptor and Signaling

IL22 Receptor Complex

IL22 signals through a heterodimeric receptor:

• IL22R1 (IL22RA1): High-affinity IL22 binding chain
• IL10R2: Shared receptor chain with IL-10, IL-20, IL-24, IL-26
• Soluble receptors: IL-22BP (IL-22 binding protein) acts as antagonist [6](https://pubmed.ncbi.nlm.nih.gov/19544425/)

Signaling Pathways

IL22 activates multiple signaling cascades:

• JAK-STAT pathway: Primarily STAT3, also STAT5
• MAPK pathway: ERK1/2 activation
• PI3K-AKT pathway: Cell survival signals
• IL-22R internalization: Receptor is internalized after activation [7](https://pubmed.ncbi.nlm.nih.gov/18836519/)

Biological Functions

Tissue Protection

IL22 exerts protective effects on epithelial tissues:

• Epithelial barrier function: Promotes tight junction proteins
• Antimicrobial defense: Induces antimicrobial peptides (RegIIIγ, S100A8/A9)
• Wound healing: Promotes cell proliferation and migration
• Mucus production: Enhances mucin production in gut and lung [8](https://pubmed.ncbi.nlm.nih.gov/19237716/)

Inflammatory Modulation

IL22 modulates inflammation in tissue-specific ways:

• Pro-inflammatory: In skin (psoriasis), gut (IBD)
• Anti-inflammatory: Promotes tissue repair and resolution
• Context-dependent: Effects vary by tissue and disease state [9](https://pubmed.ncbi.nlm.nih.gov/19544425/)

Neurological Implications

Neuroinflammation

IL22 plays complex roles in neuroinflammation:

• Multiple sclerosis: Elevated in MS lesions; dual role
• Autoimmune encephalitis: May contribute to pathogenesis
• Microglial modulation: Can affect microglial phenotype
• Blood-brain barrier: Protects BBB integrity [10](https://pubmed.ncbi.nlm.nih.gov/32844137/)

CNS Expression

IL22 and IL22R are expressed in the CNS:

• Astrocytes: Produce IL22 in response to inflammation
• Neurons: Express IL22R in some regions
• Microglia: Respond to IL22 signaling
• Oligodendrocytes: IL22R expression suggests roles in myelination [11](https://pubmed.ncbi.nlm.nih.gov/32844137/)

Disease Associations

Inflammatory Diseases

IL22 is involved in several inflammatory conditions:

• Psoriasis: IL22 promotes keratinocyte hyperproliferation
• Inflammatory bowel disease: Elevated in Crohn's disease and ulcerative colitis
• Rheumatoid arthritis: Contributes to synovial inflammation
• Asthma: Promotes airway inflammation and remodeling [12](https://pubmed.ncbi.nlm.nih.gov/19237716/)

Autoimmune CNS Disease

In neurological autoimmunity:

• Multiple sclerosis: Elevated IL22 in CSF and lesions
• Neuromyelitis optica: Associated with disease activity
• Autoimmune encephalitis: May be pathogenic
• Myasthenia gravis: Correlates with disease severity [13](https://pubmed.ncbi.nlm.nih.gov/32844137/)

Therapeutic Implications

Targeting IL22

Therapeutic strategies include:

• IL-22 agonists: Recombinant IL22 for tissue protection
• IL-22 antagonists: Antibodies for inflammatory diseases
• JAK inhibitors: Downstream blockade
• Clinical trials: In psoriasis, IBD, and COVID-19 [14](https://pubmed.ncbi.nlm.nih.gov/32844137/)

Clinical Applications

IL22-based therapies are being developed for:

• Psoriasis: IL-22 binding protein (IL-22BP) in trials
• IBD: Anti-IL22 antibodies
• COVID-19: IL-22 for lung protection
• Wound healing: Topical IL-22 formulations [15](https://clinicaltrials.gov/)

See Also

• [Interleukins](/biomarkers/interleukins)
• [Neuroinflammation](/mechanisms/neuroinflammation)
• [Multiple Sclerosis](/diseases/multiple-sclerosis)
• [JAK-STAT Signaling](/mechanisms/jak-stat-pathway)
• [Autoimmune Encephalitis](/diseases/autoimmune-encephalitis)

References

Pathway Diagram

The following diagram shows the key molecular relationships involving IL22 discovered through SciDEX knowledge graph analysis: