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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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CCL15
C-C motif chemokine ligand 15
Chromosome 17 · 17q12
NCBI Gene: 6359Ensembl: ENSG00000275528.2HGNC: HGNC:10613UniProt: Q16663
65PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
chemokine activitypositive regulation of inflammatory responsechemoattractant activityGO:0005615neurodegenerative diseasehepatocellular carcinomaesophageal squamous cell carcinomahypertriglyceridemia 2
✦AI Summary

CCL15 (C-C motif chemokine ligand 15), also known as MIP-1gamma, is a CC chemokine that functions primarily as a chemoattractant for T cells and monocytes 1. It acts mainly through CC chemokine receptor CCR1 and also binds CCR3, with proteolytically processed forms (CCL15(22-92), CCL15(25-92), CCL15(29-92)) demonstrating enhanced potency as chemoattractants. Mechanistically, CCL15 mediates immune cell recruitment and activation through CCR1-dependent signaling pathways. In allergic airway inflammation, the CCL6-CCR1 axis (human ortholog CCL15) promotes eosinophil differentiation and airway inflammation, with CCR1 antagonists effectively reducing disease severity 2. In intestinal fibrosis, MDSC-derived CCL15 activates fibroblasts via CCR1-MAPK signaling 3. CCL15 exhibits complex roles in cancer immunology. In hepatocellular carcinoma, CCL15 expression in the tumor core facilitates immunosuppression by recruiting and polarizing M2-like macrophages, with elevated CCL15 predicting poor prognosis 4. Conversely, CCL15 produced by liver cancer cells drives polarization of macrophages toward pro-tumoral SPP1+ phenotypes, establishing a tumor-promoting feedback loop 5. Circulating CCL15 associates with heart failure development, suggesting systemic inflammatory involvement 6. These findings identify CCL15-CCR1 pathway modulation as a potential therapeutic target for inflammatory diseases, fibrosis, and cancer.

Sources cited
1
CCL15 is also termed MIP-1gamma, acts via CCR1 and CCR3 receptors, and is produced by macrophages, dendritic cells, and lymphocytes
PMID: 15203102
2
CCL15 (human ortholog of mCCL6) and CCL23 are highly expressed in asthma patients; the CCL6-CCR1 axis promotes eosinophil differentiation and allergic airway inflammation, reducible by CCR1 antagonist BX471
PMID: 33640900
3
MDSC-derived human CCL15 activates fibroblasts via CCR1-MAPK signaling in intestinal fibrosis; elevated in CD patients with stenosis
PMID: 39739231
4
CCL15 is expressed in the core region of hepatocellular carcinoma, facilitates immunosuppressive microenvironment by recruiting and polarizing M2-like macrophages, and high expression predicts poor HCC prognosis
PMID: 35673582
5
CCL15 produced by liver cancer cells drives polarization of M0 macrophages toward SPP1+ macrophage phenotype, establishing a positive feedback loop promoting tumor stemness and chemoresistance
PMID: 39216547
6
Circulating CCL15 is among inflammatory proteins identified as causal for heart failure development in large-scale plasma proteomics study
PMID: 38225249
7
CCL15-CCR1 signaling pathway is involved in recruitment and polarization of tumor-associated macrophages in the tumor microenvironment
PMID: 36173487
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.29Weak
hepatocellular carcinomaOpen Targets
0.10Weak
esophageal squamous cell carcinomaOpen Targets
0.08Suggestive
hypertriglyceridemia 2Open Targets
0.07Suggestive
neoplasmOpen Targets
0.06Suggestive
liver cancerOpen Targets
0.06Suggestive
familial hypercholesterolemiaOpen Targets
0.06Suggestive
thyroid hormone metabolism, abnormal, 2Open Targets
0.05Suggestive
Barrett's esophagusOpen Targets
0.05Suggestive
sitosterolemia 2Open Targets
0.05Suggestive
Combined hyperlipidemiaOpen Targets
0.05Suggestive
homozygous familial hypercholesterolemiaOpen Targets
0.05Suggestive
hypercholesterolemia, autosomal dominant, 3Open Targets
0.04Suggestive
pancreatic triacylglycerol lipase deficiencyOpen Targets
0.04Suggestive
hyperlipidemia due to hepatic triglyceride lipase deficiencyOpen Targets
0.04Suggestive
Alzheimer diseaseOpen Targets
0.04Suggestive
hypercholesterolemia, autosomal dominant, type BOpen Targets
0.04Suggestive
esophageal adenocarcinomaOpen Targets
0.04Suggestive
colorectal cancerOpen Targets
0.04Suggestive
familial apolipoprotein C-II deficiencyOpen Targets
0.03Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CXCR5Protein interaction100%CCR3Protein interaction100%XCR1Protein interaction100%CCL2Protein interaction100%CCL4L2Protein interaction100%CCR5Protein interaction100%
Tissue Expression6 tissues
Liver
100%
Lung
4%
Brain
1%
Heart
0%
Ovary
0%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
CCL15CXCR5CCR3XCR1CCL2CCL4L2CCR5
PROTEIN STRUCTURE
Preparing viewer…
PDB7VL9 · 2.60 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.52LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.85 [0.50–1.52]
RankingsWhere CCL15 stands among ~20K protein-coding genes
  • #7,150of 20,598
    Most Researched65
  • #15,263of 17,882
    Most Constrained (LOEUF)1.52
Genes detectedCCL15
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
CC Chemokines in a Tumor: A Review of Pro-Cancer and Anti-Cancer Properties of the Ligands of Receptors CCR1, CCR2, CCR3, and CCR4.
PMID: 33182504
Int J Mol Sci · 2020
1.00
2
Role of chemokines in the crosstalk between tumor and tumor-associated macrophages.
PMID: 36173487
Clin Exp Med · 2023
0.90
3
Spatial maps of hepatocellular carcinoma transcriptomes reveal spatial expression patterns in tumor immune microenvironment.
PMID: 35673582
Theranostics · 2022
0.80
4
Eosinophil-derived chemokine (hCCL15/23, mCCL6) interacts with CCR1 to promote eosinophilic airway inflammation.
PMID: 33640900
Signal Transduct Target Ther · 2021
0.70
5
Large scale plasma proteomics identifies novel proteins and protein networks associated with heart failure development.
PMID: 38225249
Nat Commun · 2024
0.60