Details for: CCL28

Gene ID: 56477

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: CCL28

Ensembl ID: ENSG00000151882

Description: C-C motif chemokine ligand 28

Cell Significance Landscape

Associated with

Significant Cells

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

  • duct epithelial cell CL0000068
    CSI 23.31
    rCSI 34.11%
    PRS 95.02
  • acinar cell CL0000622
    CSI 18.37
    rCSI 26.94%
    PRS 96.22
  • luminal epithelial cell of mammary gland CL0002326
    CSI 9.85
    rCSI 17.89%
    PRS 95.92
  • ciliated epithelial cell CL0000067
    CSI 8.73
    rCSI 7.68%
    PRS 84.5
  • mammary gland epithelial cell CL0002327
    CSI 6.44
    rCSI 22.58%
    PRS 95.45
  • serous secreting cell of bronchus submucosal gland CL4033005
    CSI 6.28
    rCSI 35.76%
    PRS 93
  • colon epithelial cell CL0011108
    CSI 5.73
    rCSI 6%
    PRS 90.18
  • enterocyte of epithelium of large intestine CL0002071
    CSI 5.19
    rCSI 27.27%
    PRS 93.7
  • melanocyte CL0000148
    CSI 4.36
    rCSI 3.23%
    PRS 89.44
  • tracheobronchial serous cell CL0019001
    CSI 4.2
    rCSI 18.13%
    PRS 94.01
  • colonocyte CL1000347
    CSI 3.66
    rCSI 5.25%
    PRS 90.41
  • goblet cell CL0000160
    CSI 3.55
    rCSI 3.35%
    PRS 90.31
  • ionocyte CL0005006
    CSI 3.54
    rCSI 3.79%
    PRS 93.32
  • myoepithelial cell CL0000185
    CSI 3.42
    rCSI 8.65%
    PRS 94.09
  • transit amplifying cell CL0009010
    CSI 3.01
    rCSI 4.61%
    PRS 95.09
  • intestine goblet cell CL0019031
    CSI 3
    rCSI 2.66%
    PRS 90.09
  • epithelial cell CL0000066
    CSI 2.95
    rCSI 4.54%
    PRS 81.04
  • intrahepatic cholangiocyte CL0002538
    CSI 2.82
    rCSI 6.76%
    PRS 92.05
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 2.76
    rCSI 3.91%
    PRS 90.83
  • conjunctival epithelial cell CL1000432
    CSI 2.71
    rCSI 4.14%
    PRS 91.35
  • secretory cell CL0000151
    CSI 2.7
    rCSI 2.82%
    PRS 91.37
  • lung ciliated cell CL1000271
    CSI 2.65
    rCSI 3.06%
    PRS 87.51
  • fallopian tube secretory epithelial cell CL4030006
    CSI 2.58
    rCSI 2.48%
    PRS 90.98
  • mucus secreting cell CL0000319
    CSI 2.39
    rCSI 3.79%
    PRS 95.66
  • mature B cell CL0000785
    CSI 2.35
    rCSI 2.04%
    PRS 96.8
  • foveolar cell of stomach CL0002179
    CSI 2.33
    rCSI 4.95%
    PRS 93.72
  • pancreatic acinar cell CL0002064
    CSI 2.32
    rCSI 3.08%
    PRS 94.53
  • hematopoietic stem cell CL0000037
    CSI 2.31
    rCSI 1.53%
    PRS 93.48
  • transit amplifying cell of colon CL0009011
    CSI 2.24
    rCSI 2.63%
    PRS 92.16
  • ciliated cell CL0000064
    CSI 2.21
    rCSI 3.59%
    PRS 86.84
  • lung secretory cell CL1000272
    CSI 2.21
    rCSI 5.48%
    PRS 93.26
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 2.13
    rCSI 1.93%
    PRS 91.15
  • acinar cell of salivary gland CL0002623
    CSI 2.12
    rCSI 49.29%
    PRS 96.26
  • enterocyte CL0000584
    CSI 2
    rCSI 3.22%
    PRS 89.64
  • mucous neck cell CL0000651
    CSI 1.95
    rCSI 2.81%
    PRS 94.33
  • BEST4+ enteroycte CL4030026
    CSI 1.92
    rCSI 2.39%
    PRS 91.77
  • multi-ciliated epithelial cell CL0005012
    CSI 1.83
    rCSI 1.83%
    PRS 87.25
  • serous secreting cell CL0000313
    CSI 1.54
    rCSI 7.79%
    PRS 95.11
  • pancreatic ductal cell CL0002079
    CSI 1.52
    rCSI 2.95%
    PRS 93.35
  • colon goblet cell CL0009039
    CSI 1.45
    rCSI 3.46%
    PRS 93.51
  • intestinal crypt stem cell of small intestine CL0009017
    CSI 1.12
    rCSI 3.02%
    PRS 93.98
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 1.06
    rCSI 2.42%
    PRS 86.01
  • intestinal crypt stem cell of colon CL0009043
    CSI 0.57
    rCSI 4.27%
    PRS 95.84

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

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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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 [CCL28](/details-gene/56477) (C-C motif chemokine ligand 28) is a secreted protein that functions as a chemokine, a class of chemoattractant cytokines crucial for immune cell trafficking. Its primary roles involve [Cell chemotaxis](/details-go/GO:0060326), [Immune response](/details-go/GO:0006955), and direct [Antimicrobial humoral immune response mediated by antimicrobial peptide](/details-go/GO:0061844). Research has identified it as a specific ligand for the chemokine receptors CCR10 and CCR3 ([Link](https://doi.org/10.1074/jbc.m001461200); [Link](https://doi.org/10.4049/jimmunol.165.6.2943)). Expression data reveals that [CCL28](/details-gene/56477) is predominantly and highly significantly expressed by various epithelial cells, particularly those in mucosal and glandular tissues. Its strong expression in cells such as [duct epithelial cell](/details-cell/CL0000068) and [acinar cell](/details-cell/CL0000622) underscores its specialized function in mucosal immunity, where it likely mediates the homing of immune cells to these barrier surfaces. ## Cellular Roles and Expression Landscape **Overall**, the expression profile of [CCL28](/details-gene/56477) demonstrates a highly specific role in epithelial tissues that form the body's primary barriers. The gene shows the highest significance in secretory and ductal epithelial cells, with [duct epithelial cell](/details-cell/CL0000068) (CSI: 23.31) and [acinar cell](/details-cell/CL0000622) (CSI: 18.37) being the most prominent. This pattern is consistent across multiple glandular and mucosal tissues, including the mammary gland ([luminal epithelial cell of mammary gland](/details-cell/CL0002326), CSI: 9.85; [mammary gland epithelial cell](/details-cell/CL0002327), CSI: 6.44), the respiratory tract ([ciliated epithelial cell](/details-cell/CL0000067), CSI: 8.73; [serous secreting cell of bronchus submucosal gland](/details-cell/CL4033005), CSI: 6.28), and the large intestine ([colon epithelial cell](/details-cell/CL0011108), CSI: 5.73; [enterocyte of epithelium of large intestine](/details-cell/CL0002071), CSI: 5.19). This restricted and potent expression pattern in mucosal epithelial cells suggests that [CCL28](/details-gene/56477) is a key sentinel molecule, constitutively secreted at these sites to orchestrate immune surveillance by recruiting CCR10- and CCR3-expressing lymphocytes, such as IgA-secreting plasma cells and a subset of T cells. ## Pathways and Molecular Function The functional annotations for [CCL28](/details-gene/56477) are highly consistent with its role as a chemokine expressed at mucosal surfaces. Its primary molecular function is defined as [Chemokine activity](/details-go/GO:0008009), enabling it to guide the migration of specific immune cells. This activity is central to its involvement in biological processes such as [Cell chemotaxis](/details-go/GO:0060326) and the broader [Immune response](/details-go/GO:0006955). Mechanistically, [CCL28](/details-gene/56477) functions as an extracellular ligand that binds to and activates G-protein coupled receptors (GPCRs). This is reflected in its association with Reactome pathways like [Chemokine receptors bind chemokines](/details-reactome/R-HSA-380108), [Gpcr ligand binding](/details-reactome/R-HSA-500792), and [G alpha (i) signalling events](/details-reactome/R-HSA-418594). Upon binding its receptors, it triggers intracellular signaling cascades that lead to cellular adhesion and directed movement. Furthermore, [CCL28](/details-gene/56477) is annotated with direct antimicrobial functions ([Antimicrobial humoral immune response mediated by antimicrobial peptide](/details-go/GO:0061844)), suggesting it contributes to host defense not only by recruiting immune cells but also by directly targeting pathogens. ## Research Directions Based on its specific expression pattern and function, [CCL28](/details-gene/56477) presents several avenues for further investigation, particularly concerning its role in both homeostasis and disease at mucosal sites. **Testable Hypotheses:** 1. Given its exceptionally high significance in [duct epithelial cell](/details-cell/CL0000068) and [acinar cell](/details-cell/CL0000622) of exocrine glands, dysregulation of [CCL28](/details-gene/56477) may be a key pathogenic factor in autoimmune diseases like Sjögren's syndrome, where aberrant lymphocyte infiltration leads to glandular destruction. Overexpression of [CCL28](/details-gene/56477) could drive the chronic recruitment of pathogenic CCR10+ lymphocytes to salivary and lacrimal glands. 2. The high expression of [CCL28](/details-gene/56477) in [luminal epithelial cell of mammary gland](/details-cell/CL0002326) suggests it is a component of human breast milk. Secreted [CCL28](/details-gene/56477) could play a vital role in establishing the neonatal gut mucosal immune system by recruiting maternal IgA-producing B cells or by shaping the infant's own immune cell populations in the intestine. **Proposed Experiment:** To test the first hypothesis regarding Sjögren's syndrome, a preclinical study could be conducted using a non-obese diabetic (NOD) mouse model, which spontaneously develops a Sjögren's-like disease. One cohort of mice would be treated with a systemic neutralizing antibody against [CCL28](/details-gene/56477) prior to and during disease development, while a control cohort receives an isotype control antibody. The therapeutic effect would be assessed by measuring salivary flow rates, quantifying lymphocyte infiltration (specifically T cells and B cells) in salivary gland tissue via histology and flow cytometry, and analyzing the local cytokine and autoantibody profiles. A reduction in glandular inflammation and restoration of function in the anti-CCL28 treated group would validate its role in disease pathogenesis. **Therapeutic Potential:** As a secreted protein, [CCL28](/details-gene/56477) is an accessible therapeutic target. For autoimmune conditions characterized by excessive immune cell infiltration into mucosal tissues (e.g., Sjögren's syndrome, inflammatory bowel disease), **inhibition** of the CCL28-CCR10 axis represents a promising strategy. This could be achieved using monoclonal antibodies against [CCL28](/details-gene/56477) or small molecule antagonists targeting its receptor, CCR10. Conversely, for situations requiring enhanced mucosal immunity, such as in response to certain infections or for vaccine adjuvant development, local **activation** or delivery of recombinant [CCL28](/details-gene/56477) could be explored to boost the recruitment of effector immune cells to mucosal sites.

Genular Protein ID: 4198799954

Symbol: CCL28_HUMAN

Name: C-C motif chemokine 28

UniProtKB Accession Codes:

Q9NRJ3 D7RIE7

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BMRB 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChiTaRS 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 DisProt 1 EMBL 7 Ensembl 2 ExpressionAtlas 1 GO 10 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PDB 1 PDBsum 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 Reactome 2 RefSeq 3 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 10781587

Title: Identification of a novel chemokine (CCL28), which binds CCR10 (GPR2).

PubMed ID: 10781587

DOI: 10.1074/jbc.m001461200

PubMed ID: 10975800

Title: A novel chemokine ligand for CCR10 and CCR3 expressed by epithelial cells in mucosal tissues.

PubMed ID: 10975800

DOI: 10.4049/jimmunol.165.6.2943

PubMed ID: 15372022

Title: The DNA sequence and comparative analysis of human chromosome 5.

PubMed ID: 15372022

DOI: 10.1038/nature02919

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: 127
  • Mass: 14280
  • Checksum: 3E8551A63A2C8D62
  • Sequence:
    • MQQRGLAIVA LAVCAALHAS EAILPIASSC CTEVSHHISR RLLERVNMCR IQRADGDCDL 
AAVILHVKRR RICVSPHNHT VKQWMKVQAA KKNGKGNVCH RKKHHGKRNS NRAHQGKHET 
YGHKTPY

Genular Protein ID: 4254544595

Symbol: D6RC73_HUMAN

Name: N/A

UniProtKB Accession Codes:

D6RC73

Database IDs:

ARBA 3 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 3 Ensembl 2 GO 3 Gene3D 1 GeneTree 1 HGNC 1 HOGENOM 1 InterPro 2 NCBI Taxonomy 1 OMA 1 OrthoDB 1 PeptideAtlas 1 Pfam 2 Proteomes 2 ProteomicsDB 2 RefSeq 1 SAM 1 SUPFAM 1 UCSC 1 VEuPathDB 1

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

PubMed ID: 11181995

Title: The sequence of the human genome.

PubMed ID: 11181995

DOI: 10.1126/science.1058040

PubMed ID: 15372022

Title: The DNA sequence and comparative analysis of human chromosome 5.

PubMed ID: 15372022

DOI: 10.1038/nature02919

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

Sequence Information:

  • Length: 80
  • Mass: 9258
  • Checksum: C72BEBA47633A762
  • Sequence:
    • MCRIQRADGD CDLAAVILHV KRRRICVSPH NHTVKQWMKV QAAKKNGKGN VCHRKKHHGK 
RNSNRAHQGK HETYGHKTPY