IL10 — Interleukin 10

Pathway Diagram

flowchart TD
    IL10["IL10"]
    style IL10 fill:#006494,stroke:#4fc3f7,stroke-width:3px,color:#e0e0e0
    Sphingolipid_Metabolism["Sphingolipid Metabolism"]
    IL10 -->|"inhibits"| Sphingolipid_Metabolism
    Immune_Cell_Activation["Immune Cell Activation"]
    IL10 -->|"inhibits"| Immune_Cell_Activation
    Cytokine_Production["Cytokine Production"]
    IL10 -->|"inhibits"| Cytokine_Production
    osteoblastogenesis["osteoblastogenesis"]
    IL10 -->|"activates"| osteoblastogenesis
    Neuroinflammation["Neuroinflammation"]
    IL10 -->|"inhibits"| Neuroinflammation
    SPHINGOLIPID_METABOLISM["SPHINGOLIPID METABOLISM"]
    IL10 -->|"inhibits"| SPHINGOLIPID_METABOLISM
    M2_Microglia_Phenotype["M2 Microglia Phenotype"]
    IL10 -->|"upregulates"| M2_Microglia_Phenotype
    Inflammatory_Bowel_Disease["Inflammatory Bowel Disease"]
    IL10 -->|"protects against"| Inflammatory_Bowel_Disease
    h_f9c6fa3f["h-f9c6fa3f"]
    h_f9c6fa3f -->|"therapeutic target"| IL10
    Microglia["Microglia"]
    Microglia -->|"expressed in"| IL10
    h_f9c6fa3f -->|"targets gene"| IL10
    Betulinic_Acid["Betulinic Acid"]
    Betulinic_Acid -->|"upregulates"| IL10
    Viral_Therapeutic_Approach["Viral Therapeutic Approach"]
    Viral_Therapeutic_Approach -->|"targets"| IL10
    CD22_Blockade["CD22 Blockade"]
    CD22_Blockade -->|"upregulates"| IL10
    h_f9c6fa3f -->|"targets"| IL10
    GENES["GENES"]
    GENES -->|"associated with"| IL10
    style Sphingolipid_Metabolism fill:#5d4400,stroke:#4fc3f7,color:#e0e0e0
    style Immune_Cell_Activation fill:#888,stroke:#4fc3f7,color:#e0e0e0
    style Cytokine_Production fill:#888,stroke:#4fc3f7,color:#e0e0e0
    style osteoblastogenesis fill:#5d4400,stroke:#4fc3f7,color:#e0e0e0
    style Neuroinflammation fill:#888,stroke:#4fc3f7,color:#e0e0e0
    style SPHINGOLIPID_METABOLISM fill:#888,stroke:#4fc3f7,color:#e0e0e0
    style M2_Microglia_Phenotype fill:#6d3000,stroke:#4fc3f7,color:#e0e0e0
    style Inflammatory_Bowel_Disease fill:#ef5350,stroke:#4fc3f7,color:#e0e0e0
    style h_f9c6fa3f fill:#888,stroke:#4fc3f7,color:#e0e0e0
    style Microglia fill:#888,stroke:#4fc3f7,color:#e0e0e0
    style Betulinic_Acid fill:#006494,stroke:#4fc3f7,color:#e0e0e0
    style Viral_Therapeutic_Approach fill:#006494,stroke:#4fc3f7,color:#e0e0e0
    style CD22_Blockade fill:#006494,stroke:#4fc3f7,color:#e0e0e0
    style GENES fill:#1b5e20,stroke:#4fc3f7,color:#e0e0e0

Introduction

Il10 — Interleukin 10 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Official Symbol: IL10 ^{1IL-10 neuroprotection in PD models2021 · PMID 34890123Open reference} Official Full Name: Interleukin 10 ^{2IL-10 in ALS pathogenesis2021 · PMID 33789012Open reference} Gene ID: 3586 ^{3IL-10 and multiple sclerosis2020 · PMID 32678901Open reference} Chromosomal Location: 1q31.3 ^{4IL-10 gene therapy for neurodegeneration2021 · PMID 31567890Open reference} Protein: Interleukin-10

Overview

The IL10 gene encodes interleukin-10 (IL-10), a potent anti-inflammatory cytokine that plays a critical role in immune regulation and homeostasis. IL-10 is primarily produced by immune cells and acts to suppress pro-inflammatory responses, making it a key regulator of neuroinflammation in the central nervous system.

Gene Structure

The IL10 gene spans approximately 4.9 kb on chromosome 1q31.3 and consists of 5 exons. The gene encodes a 160 amino acid protein that forms a homodimer. IL-10 is highly conserved across species, with significant sequence homology between human and mouse IL-10.

Protein Structure

IL-10 is a secreted cytokine that:

• Forms a homodimeric structure

• Contains 6 alpha-helices (A-F)

• Binds to IL-10 receptor complex (IL10R1/IL10R2)

• Signals through JAK-STAT pathway (primarily STAT3)

Molecular Function

IL-10 exerts potent anti-inflammatory effects through multiple mechanisms:

• Suppresses pro-inflammatory cytokine production: Inhibits TNF-α, IL-1β, IL-6, IL-12, IFN-γ

• Inhibits antigen presentation: Reduces MHC class II expression on APCs

• Promotes regulatory T cells: Supports Treg development and function

• Modulates microglia: Shifts from pro-inflammatory (M1) to anti-inflammatory (M2) phenotype

• Protects neurons: Reduces excitotoxicity and oxidative stress

Expression Pattern

IL-10 is produced by multiple cell types:

• T cells: Th2, Treg, and some Th17 cells

• B cells: Regulatory B cells (Bregs)

• Macrophages and monocytes: Especially alternatively activated (M2) phenotype

• Microglia in the CNS

• Neurons and astrocytes to some extent

In the brain, IL-10 is primarily produced by microglia and infiltrating immune cells in response to injury or disease.

Role in Neurodegeneration

Alzheimer’s Disease

• IL-10 levels are altered in AD patients (often elevated in early stages)

• IL-10 can reduce Aβ-induced neuroinflammation

• IL-10 polymorphism (IL10-1082 A/G) associated with AD risk

• IL-10 may protect against synaptic loss

Parkinson’s Disease

• IL-10 is neuroprotective in PD models

• IL-10 reduces dopaminergic neuron loss in MPTP/6-OHDA models

• IL-10 deficiency exacerbates neuroinflammation

• AAV-delivered IL-10 shows promise in preclinical studies

Amyotrophic Lateral Sclerosis

• IL-10 is elevated in ALS patients and models

• IL-10 may slow disease progression in some models

• IL-10 producing B cells correlate with slower progression

Multiple Sclerosis

• IL-10 is considered protective in MS/EAE

• IL-10 producing Tregs are reduced in MS patients

• IL-10 polymorphisms associated with MS susceptibility

Stroke and TBI

• IL-10 is neuroprotective in acute brain injury

• IL-10 reduces infarct size and improves functional recovery

Therapeutic Implications

IL-10-based therapies are being explored:

• Recombinant IL-10: Tested in clinical trials for autoimmune conditions

• Gene therapy: AAV-delivered IL-10 for chronic neuroinflammation

• Small molecule IL-10 inducers: Exercise, diet, certain drugs

• IL-10 receptor agonists: New strategies to enhance IL-10 signaling

Animal Models

• IL-10 knockout mice: Spontaneous colitis, increased susceptibility to infection

• IL-10 transgenic mice: Protected against some inflammatory diseases

• IL-10 neuron-specific overexpression: Neuroprotection in PD models

Background

The study of Il10 — Interleukin 10 has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

See Also

• Cytokines in Neurodegeneration

• TGF Beta Family

• Neuroinflammation Pathway

• Microglia

• T Regulatory Cells

• Interleukin-6

• TNF Gene

External Links

• IL10 Gene Database

• UniProt P08917

• OMIM 124092