Details for: CCL16

Gene ID: 6360

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: CCL16

Ensembl ID: ENSG00000275152

Description: C-C motif chemokine ligand 16

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • hepatocyte CL0000182
    CSI 4.36
    rCSI 7.8%
    PRS 99.94
  • periportal region hepatocyte CL0019026
    CSI 3.78
    rCSI 14.72%
    PRS 100
  • centrilobular region hepatocyte CL0019029
    CSI 3.52
    rCSI 9.19%
    PRS 100

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary C-C motif chemokine ligand 16 ([CCL16](/details-gene/6360)), also known as Liver-Expressed Chemokine (LEC) or HCC-4, is a secreted protein that functions as a chemoattractant for various immune cells, including lymphocytes and monocytes ([Link](https://pubmed.ncbi.nlm.nih.gov/9642106/)). It belongs to the CC chemokine family and plays a significant role in inflammatory responses, cell-cell signaling, and chemotaxis by binding to and activating G-protein coupled chemokine receptors. Expression data indicates that **Overall**, [CCL16](/details-gene/6360) is a highly significant and specific marker for liver parenchymal cells, particularly [hepatocytes](/details-cell/CL0000182), suggesting a primary role in modulating the immune landscape of the liver under both homeostatic and pathological conditions. ## Cellular Roles and Expression Landscape The expression profile of [CCL16](/details-gene/6360) demonstrates a pronounced tissue specificity for the liver. **Overall**, the gene shows the highest significance in [hepatocytes](/details-cell/CL0000182) (CSI: 4.36), with strong signals also observed in functionally distinct hepatocyte subpopulations, including [periportal region hepatocytes](/details-cell/CL0019026) (CSI: 3.78) and [centrilobular region hepatocytes](/details-cell/CL0019029) (CSI: 3.52). This robust and specific expression pattern suggests that [hepatocytes](/details-cell/CL0000182) are a primary source of this chemokine. While expressed at a basal level, its production can be regulated by cytokines such as interleukin-10 ([Link](https://pubmed.ncbi.nlm.nih.gov/9596672/)). As a chemokine, its secretion by [hepatocytes](/details-cell/CL0000182) into the extracellular space likely plays a critical role in orchestrating the recruitment and positioning of immune cells within the liver sinusoids, contributing to immune surveillance and the initiation of inflammatory responses. ## Pathways and Molecular Function The functional annotations for [CCL16](/details-gene/6360) are consistent with its identity as a classic chemokine. Its molecular function is defined by its [chemokine activity](/details-go/GO0008009) and its ability to bind C-C motif chemokine receptors ([GO:0048020](https://www.ebi.ac.uk/QuickGO/term/GO:0048020)), initiating downstream signaling cascades. This activity is part of the broader Reactome pathway for [Chemokine receptors bind chemokines](/details-reactome/R-HSA-380108). Biologically, [CCL16](/details-gene/6360) is involved in processes central to immunity and inflammation. It mediates the directed migration of immune cells through [chemotaxis](/details-go/GO0006935), including [eosinophil chemotaxis](/details-go/GO0048245), and contributes to the general [inflammatory response](/details-go/GO0006954). Its signaling occurs through G-protein coupled receptors, as indicated by its annotation to pathways like [G alpha (i) signalling events](/details-reactome/R-HSA-418594) and [Signaling by GPCR](/details-reactome/R-HSA-372790). The secretion of [CCL16](/details-gene/6360) into the [extracellular space](/details-go/GO0005615) allows it to function as a soluble mediator, guiding immune cells to sites of inflammation or tissue surveillance within the liver. ## Research Directions The specific expression of [CCL16](/details-gene/6360) in [hepatocytes](/details-cell/CL0000182) combined with its function as an immune chemoattractant points toward a critical role in liver immunobiology. This provides a foundation for several testable hypotheses. 1. **Hypothesis 1:** Under homeostatic conditions, low-level constitutive secretion of [CCL16](/details-gene/6360) by [hepatocytes](/details-cell/CL0000182) is essential for maintaining the resident populations of liver-associated immune cells, such as Kupffer cells and lymphocytes, thereby contributing to hepatic immune surveillance. 2. **Hypothesis 2:** In the context of chronic liver diseases like non-alcoholic steatohepatitis (NASH), stressed [hepatocytes](/details-cell/CL0000182) significantly upregulate [CCL16](/details-gene/6360) expression, creating a chemotactic gradient that drives the pathological infiltration of inflammatory monocytes and lymphocytes, which in turn promotes fibrosis and tissue damage. To test the second hypothesis regarding its role in NASH, a key experiment could be proposed. A hepatocyte-specific knockout of `Ccl16` could be generated in mice, which would then be placed on a diet known to induce NASH. The degree of liver inflammation, immune cell infiltration (analyzed by flow cytometry and immunohistochemistry), steatosis, and fibrosis (assessed by histology and gene expression markers) would be compared between knockout and wild-type control animals. A significant reduction in these pathological features in the knockout mice would confirm that hepatocyte-derived [CCL16](/details-gene/6360) is a key driver of disease progression. Given that [CCL16](/details-gene/6360) is a secreted protein and a pro-inflammatory mediator, it represents a plausible therapeutic target. **Inhibition**, rather than activation, would be the therapeutic goal. A monoclonal antibody or a small molecule inhibitor targeting [CCL16](/details-gene/6360) or its primary receptor could be developed to block its chemoattractant activity. Such a therapeutic could potentially reduce the harmful accumulation of inflammatory cells in the liver during chronic diseases, making it a candidate for treating conditions like NASH or alcoholic hepatitis where inflammation is a central pathological mechanism.

Genular Protein ID: 1602645769

Symbol: CCL16_HUMAN

Name: C-C motif chemokine 16

UniProtKB Accession Codes:

O15467 Q4KKU0

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 DIP 1 DNASU 1 DisGeNET 1 EMBL 8 Ensembl 2 ExpressionAtlas 1 GO 13 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 3 PDBsum 3 PIR 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 2 RefSeq 2 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TopDownProteomics 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 neXtProt 1

Citations:

PubMed ID: 9596672

Title: Characterization of a novel CC chemokine, HCC-4, whose expression is increased by interleukin-10.

PubMed ID: 9596672

PubMed ID: 9545580

Title: Isolation of cDNA encoding a novel human CC chemokine NCC-4/LEC.

PubMed ID: 9545580

DOI: 10.1016/s0167-4781(97)00235-2

PubMed ID: 10213461

Title: Organization of the chemokine gene cluster on human chromosome 17q11.2 containing the genes for CC chemokine MPIF-1, HCC-2, LEC, and RANTES.

PubMed ID: 10213461

DOI: 10.1089/107999099314153

PubMed ID: 9642106

Title: Isolation and characterization of LMC, a novel lymphocyte and monocyte chemoattractant human CC chemokine, with myelosuppressive activity.

PubMed ID: 9642106

DOI: 10.1006/bbrc.1998.8762

PubMed ID: 10235110

Title: Genomic organization of the genes for human and mouse CC chemokine LEC.

PubMed ID: 10235110

DOI: 10.1089/104454999315330

PubMed ID: 10671294

Title: Cloning, characterization and genomic organization of LCC-1 (scya16), a novel human CC chemokine expressed in liver.

PubMed ID: 10671294

DOI: 10.1006/cyto.1999.0548

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

Sequence Information:

  • Length: 120
  • Mass: 13600
  • Checksum: 373D73016134D894
  • Sequence:
    • MKVSEAALSL LVLILIITSA SRSQPKVPEW VNTPSTCCLK YYEKVLPRRL VVGYRKALNC 
HLPAIIFVTK RNREVCTNPN DDWVQEYIKD PNLPLLPTRN LSTVKIITAK NGQPQLLNSQ