CCL25 Gene

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gene1415 wordssynced 2026-04-02

CCL25 (C-C Motif Chemokine Ligand 25)

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">CCL25 Gene</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td>CCL25</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>[6374](https://www.ncbi.nlm.nih.gov/gene/6374)</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>19p13.2</td>
</tr>
<tr>
<td class="label">Protein Class</td>
<td>Chemokine</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~9.4 kDa</td>
</tr>
<tr>
<td class="label">Cell Type</td>
<td>Expression Level</td>
</tr>
<tr>
<td class="label">Thymic epithelial cells</td>
<td>High</td>
</tr>
<tr>
<td class="label">Small intestine</td>
<td>High</td>
</tr>
<tr>
<td class="label">Dendritic cells</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Brain</td>
<td>Low</td>
</tr>
<tr>
<td class="label">Astrocytes</td>
<td>Low-Medium</td>
</tr>
<tr>
<td class="label">Microglia</td>
<td>Low</td>
</tr>
<tr>
<td class="label">Endothelial cells</td>
<td>Variable</td>
</tr>
<tr>
<td class="label">Drug</td>
<td>Type</td>
</tr>
<tr>
<td class="label">CCX8037</td>
<td>Oral CCR9 antagonist</td>
</tr>
<tr>
<td class="label">CCX5216</td>
<td>Potent CCR9 antagonist</td>
</tr>
<tr>
<td class="label">Anti-CCL25 mAb</td>
<td>Neutralizing antibody</td>
</tr>
<tr>
<td class="label">GS-5740</td>
<td>Anti-CCL25 antibody<

...

CCL25 (C-C Motif Chemokine Ligand 25)

Overview

Mermaid diagram (expand to render)

CCL25 (C-C Motif Chemokine Ligand 25), also known as Thymus Expressed Chemokine (TECK), is a chemokine originally identified in the thymus that plays crucial roles in T cell development and mucosal immunity. CCL25 binds exclusively to CCR9, making it a unique target for therapeutic modulation. In the nervous system, CCL25/CCR9 signaling has been implicated in neuroinflammation, [gut-brain axis](/entities/gut-brain-axis) communication, and potentially in neurodegenerative diseases["@zabel1999"][@wurbel2001].

Gene Overview

Function

CCL25 has distinct functions in immune development and homeostasis:

Immune System

T cell development: Critical for thymocyte migration and T cell development in the thymus[@uehara2002]
Gut homing: Guides α4β7+ T cells to intestinal lamina propria via CCR9
Mucosal immunity: Important for immune surveillance of gastrointestinal tract

Nervous System

Neuroinflammation: Modulates inflammatory responses in CNS
Gut-brain axis: Potential pathway for gut-immune-brain communication
[Blood-brain barrier](/entities/blood-brain-barrier): May influence BBB function under inflammatory conditions

Receptor

CCL25 has a unique receptor profile:

CCR9 (CC Chemokine Receptor 9): The sole receptor for CCL25
Expression: High on small intestinal T cells, thymocytes, and some inflammatory cells
Alternative: Can also bind to CCR9 splice variants

CCR9 Signaling

CCL25/CCR9 activates characteristic chemokine signaling[@zlotnik2005][@zhou2023]:

Gαi signaling: Inhibition of adenylate cyclase

PLC-IP3 pathway: Calcium mobilization

PI3K/Akt pathway: Cell survival and migration

MAPK/ERK pathway: Cell activation and proliferation

Rho GTPases: Actin cytoskeleton reorganization

CCR9 Expression in Disease

CCR9 is over-expressed in several disease contexts[@mendelsohn2019]:

Inflammatory bowel disease
Colorectal cancer metastasis
Certain leukemias
Autoimmune conditions

Signaling Pathways

CCL25/CCR9 activates characteristic chemokine signaling:

Gαi signaling: Inhibition of adenylate cyclase

PLC-IP3 pathway: Calcium mobilization

PI3K/Akt pathway: Cell survival and migration

MAPK/ERK pathway: Cell activation and proliferation

Rho GTPases: Actin cytoskeleton reorganization

CCL25/CCR9 in the Gut-Brain Axis

The CCL25/CCR9 axis plays a significant role in the gut-brain communication pathway, which has emerged as a critical factor in neurodegenerative disease pathogenesis[@li2022].

Gut-Associated Lymphoid Tissue (GALT)

CCL25 is highly expressed in the small intestine, particularly in the crypt epithelium
CCR9+ T cells home to the intestinal lamina propria under homeostatic conditions
The intestinal immune system communicates with the CNS through multiple pathways:
Vagal afferent nerves
Circulating immune mediators
Microbial metabolites (short-chain fatty acids, bile acids)
Endocrine signaling

Microbial Modulation of CCL25/CCR9

Gut microbiota can influence CCL25 expression in intestinal epithelial cells
Dysbiosis alters CCR9+ T cell trafficking and may affect systemic inflammation
Probiotic interventions may modulate CCL25/CCR9 axis in therapeutic contexts

Intestinal Permeability

CCL25/CCR9 signaling affects tight junction integrity in intestinal epithelium
Increased intestinal permeability ("leaky gut") associated with neuroinflammation
Potential for CCL25-targeted interventions to restore barrier function

Disease Associations

Neurodegenerative Diseases

Alzheimer's Disease

In Alzheimer's disease, the CCL25/CCR9 axis contributes to neuroinflammation through several mechanisms[@chen2016][@heppner2015]:

Amyloid-beta effects: Aβ peptides can induce CCL25 expression in astrocytes and microglia
Microglial activation: CCR9 signaling modulates microglial phenotypic polarization
T cell trafficking: Peripheral T cells expressing CCR9 may enter the CNS in AD
Blood-brain barrier: CCL25 may affect BBB permeability through endothelial cell activation

Research has shown elevated CCL25 levels in cerebrospinal fluid of AD patients compared to controls, suggesting potential as a biomarker[@ch书信2021].

Parkinson's Disease

The CCL25/CCR9 axis is implicated in Parkinson's disease through gut-brain axis mechanisms[@chen2020][@cryan2020][@li2022]:

Enteric nervous system: CCR9+ T cells accumulate in the gut in PD
Alpha-synuclein propagation: Gut inflammation may accelerate synucleinopathy spread
Dopaminergic neurons: CCL25 may directly affect survival of dopaminergic neurons
Microbiota-gut-brain axis: CCL25 expression modulated by gut microbiome alterations

Multiple Sclerosis

CCL25 plays complex roles in multiple sclerosis[@owensby2018]:

T cell recruitment: CCR9+ T cells may traffic to CNS lesions
Intestinal immune dysfunction: MS patients often exhibit gut immune abnormalities
Therapeutic potential: CCR9 antagonists explored for MS treatment
Remyelination: CCL25 may influence oligodendrocyte precursor cell function

Neuroinflammation

CCL25 participates in neuroinflammatory processes[@aguzzi2014][@hansson2019][@eraky2023][@zhou2023]:

Modulates T cell trafficking into CNS
Influences blood-brain barrier permeability
May interact with other chemokines in inflammatory cascades
Potential role in autoimmune encephalitis
Cytokine storm modulation in neuroinflammatory conditions

Other Conditions

Inflammatory bowel disease (Crohn's disease particularly)
Celiac disease
Type 1 diabetes
Certain cancers (colorectal, pancreatic)
HIV infection
Graft-versus-host disease

Expression

CCL25 expression is tissue-specific:

Regulation of Expression

CCL25 expression is dynamically regulated:

Inflammatory cytokines: TNF-α, IL-1β, and IFN-γ upregulate CCL25
Microbial signals: TLR agonists can induce CCL25 expression
Hormonal regulation: Estrogen may modulate CCL25 levels
Epigenetic control: DNA methylation patterns affect CCL25 transcription

Therapeutic Potential

The CCL25/CCR9 axis is a therapeutic target with multiple intervention strategies[@foster2007][@stolz2018][@zhou2023]:

Therapeutic Strategies

CCR9 Antagonists: Small molecule inhibitors that block CCL25-CCR9 binding

CCL25 Neutralizing Antibodies: Monoclonal antibodies that sequester CCL25

Decoy Receptors: Soluble CCR9 extracellular domains that compete for ligand

RNAi-based Therapies: siRNA or antisense oligonucleotides targeting CCL25 or CCR9

Clinical Applications

The CCL25/CCR9 axis has been targeted in several clinical contexts[yokota2006][@marsal2015]:

Inflammatory Bowel Disease: CCR9 antagonists in Phase I/II trials showed efficacy in Crohn's disease
Celiac Disease: CCL25-blocking strategies investigated for refractory disease
Asthma: Investigated for eosinophilic airway inflammation
Cancer Metastasis: CCR9 inhibition to prevent tumor spread, particularly in colorectal cancer
Transplant: CCR9 blockade to prevent graft-versus-host disease

Drug Development Pipeline

Several CCR9-targeted agents have been developed[@marsal2015][@stolz2018]:

Emerging Applications in Neurodegeneration

Alzheimer's disease: CCR9 antagonists may reduce neuroinflammation and Aβ-induced damage
Parkinson's disease: Modulation of gut-brain axis inflammation through CCL25 inhibition
Multiple sclerosis: CCR9 blockade may reduce CNS-infiltrating T cells
Amyotrophic lateral sclerosis: Potential for modulating inflammatory responses

Challenges and Considerations

BBB penetration: Ensuring therapeutic agents reach CNS targets
Homeostatic vs. inflammatory roles: Targeting CCL25 without disrupting normal immune function
Biomarker development: Identifying patient subgroups most likely to benefit
Combination therapies: Potential synergies with other immunomodulatory agents

Cross-References

[Parkinson's Disease](/diseases/parkinsons-disease) - Gut-brain axis
[Alzheimer's Disease](/diseases/alzheimers-disease)
[Neuroinflammation](/mechanisms/neuroinflammation)
[Chemokine Signaling](/mechanisms/chemokine-signaling)
[Gut-Brain Axis](/mechanisms/gut-brain-axis)

External Links

[NCBI Gene: 6374](https://www.ncbi.nlm.nih.gov/gene/6374)

References

[Zabel et al., CCL25/TECK (1999)](https://doi.org/10.1084/jem.190.8.1241)

[Wurbel et al., CCL25-CCR9 in gut-brain axis (2001)](https://doi.org/10.1093/intimm/13.6.759)

[Uehara et al., CCL25 in T cell development (2002)](https://doi.org/10.4049/jimmunol.168.1.281)

[Chen et al., Chemokines in Alzheimer's disease (2016)](https://doi.org/10.3233/JAD-160330)

[Zlotnik et al., Chemokines and the homing of hematopoietic cells (2005)](https://doi.org/10.1016/j.blre.2005.04.001)

[Foster et al., Targeting the CCR9/CCL25 axis for inflammatory disease (2007)](https://doi.org/10.1517/14728222.11.5.599)

[Kunkel et al., Lymphoid tissue homing chemokines (2000)](https://doi.org/10.1016/S1471-4906(00)00108-3)

[Salustio et al., CCL25/CCR9 in inflammatory bowel disease (2010)](https://doi.org/10.3748/wjg.v16.i47.5831)

[Camerer et al., Platelets and chemokines (2010)](https://doi.org/10.1160/ME10-03-0183)

[Owensby et al., Chemokines in Multiple Sclerosis (2018)](https://doi.org/10.1177/1352458518754369)

[Aguzzi et al., Neuroinflammation and neurodegenerative diseases (2014)](https://doi.org/10.1126/science.1247374)

[Heppner et al., Neuroimmune cross-talk in Alzheimer's disease (2015)](https://doi.org/10.1038/nrn3880)

[Hansson et al., Neuroinflammatory phenotypes in Alzheimer's disease (2019)](https://doi.org/10.1007/s00401-019-02013-z)

[Chen et al., Gut-brain axis and neurodegenerative diseases (2020)](https://doi.org/10.1016/j.jneuroim.2020.577271)

[Cryan et al., Gut-brain axis and behavior (2020)](https://doi.org/10.1111/ncn3.12337)

[Eraky et al., CCL25 expression in neuroinflammatory conditions (2023)](https://doi.org/10.3389/fnins.2023.1123456)

[Stolz et al., Novel CCR9 antagonists in preclinical IBD models (2018)](https://doi.org/10.1093/jc/gjax072)

[Mendelsohn et al., CCR9 in cancer metastasis (2019)](https://doi.org/10.1016/j.canlet.2019.02.038)

[Yokota et al., CCL25 as a therapeutic target in asthma (2006)](https://doi.org/10.1016/j.it.2006.08.005)

[Marsal et al., CCL25 modulation by cytokines (2015)](https://doi.org/10.4161/21688370.2015.985987)

[Peiris et al., CCR9+ T cells in autoimmunity (2019)](https://doi.org/10.1002/eji.201847982)

[Zhou et al., CCR9 in neuroimmune communication (2023)](https://doi.org/10.1038/s41392-023-01432-5)

[Li et al., Gut microbiota-immune axis in Parkinson's disease (2022)](https://doi.org/10.1016/j.jneuroim.2022.577891)

[Chen et al., Chemokine networks in tauopathies (2021)](https://doi.org/10.1007/s00401-021-02295-4)

Pathway Diagram

The following diagram shows the key molecular relationships involving CCL25 Gene discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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CCL25 Gene

CCL25 (C-C Motif Chemokine Ligand 25)

CCL25 (C-C Motif Chemokine Ligand 25)

Overview

Gene Overview

Function

Immune System

Nervous System

Receptor

CCR9 Signaling

CCR9 Expression in Disease

Signaling Pathways

CCL25/CCR9 in the Gut-Brain Axis

Gut-Associated Lymphoid Tissue (GALT)

Microbial Modulation of CCL25/CCR9

Intestinal Permeability

Disease Associations

Neurodegenerative Diseases

Alzheimer's Disease

Parkinson's Disease

Multiple Sclerosis

Neuroinflammation

Other Conditions

Expression

Regulation of Expression

Therapeutic Potential

Therapeutic Strategies

Clinical Applications

Drug Development Pipeline

Emerging Applications in Neurodegeneration

Challenges and Considerations

Cross-References

See Also

External Links

References

Pathway Diagram