Details for: CXCL13

Gene ID: 10563

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: CXCL13

Ensembl ID: ENSG00000156234

Description: C-X-C motif chemokine ligand 13

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • T follicular helper cell CL0002038
    CSI 22.43
    rCSI 16.78%
    PRS 99.65
  • naive thymus-derived CD8-positive, alpha-beta T cell CL0000900
    CSI 11.56
    rCSI 8.12%
    PRS 100
  • CD8-positive, CD28-negative, alpha-beta regulatory T cell CL0000920
    CSI 10.55
    rCSI 21.04%
    PRS 99.87
  • VIP GABAergic cortical interneuron CL4023016
    CSI 9.38
    rCSI 11.2%
    PRS 98.99
  • activated CD8-positive, alpha-beta T cell, human CL0001049
    CSI 4.19
    rCSI 7.17%
    PRS 99.88
  • stromal cell CL0000499
    CSI 2.01
    rCSI 5.64%
    PRS 99.66
  • follicular dendritic cell CL0000442
    CSI 1.72
    rCSI 27.61%
    PRS 99.51
  • exhausted T cell CL0011025
    CSI 1.44
    rCSI 24.32%
    PRS 99.19
  • mesenchymal lymphangioblast CL0005021
    CSI 0.98
    rCSI 25.64%
    PRS 99.8

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.

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  • Node Color (Target Cell CSI, relative to current network):
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    • High
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    • 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 [CXCL13](/details-gene/10563) (C-X-C motif chemokine ligand 13) is a protein-coding gene located on chromosome 4q21.1. It encodes a small secreted cytokine belonging to the CXC chemokine family. Primarily known as B-cell-attracting chemokine 1 (BCA-1), its principal function is to direct the migration of B lymphocytes and specific T cell subsets by binding to its receptor, CXCR5. Evidence strongly supports its critical role in the organization of secondary lymphoid organs, particularly in the formation and maintenance of B cell follicles and germinal centers. The expression data highlights its exceptional significance in [T follicular helper cells](/details-cell/CL0002038), underscoring its central function in orchestrating humoral immunity. ## Cellular Roles and Expression Landscape The expression profile of [CXCL13](/details-gene/10563) points to a highly specialized role within the adaptive immune system, particularly in the context of lymphoid tissue organization and T cell function. **Overall**, the gene exhibits its highest significance in [T follicular helper cells](/details-cell/CL0002038) (CSI: 22.43), which is consistent with their primary function of providing help to B cells within germinal centers. Its high significance is also noted in several other T cell subsets, including [naive thymus-derived CD8-positive, alpha-beta T cells](/details-cell/CL0000900) (CSI: 11.56), [CD8-positive, CD28-negative, alpha-beta regulatory T cells](/details-cell/CL0000920) (CSI: 10.55), and [activated CD8-positive, alpha-beta T cells, human](/details-cell/CL0001049) (CSI: 4.19). This pattern suggests a broader role for [CXCL13](/details-gene/10563) in T cell biology beyond its canonical function in T follicular helper cells. Furthermore, its notable expression in [stromal cells](/details-cell/CL0000499) and [follicular dendritic cells](/details-cell/CL0000442) reinforces its role as a key architectural chemokine, essential for creating the microenvironment that supports lymphocyte organization and interaction in lymphoid tissues. Intriguingly, a high CSI value is also observed in [VIP GABAergic cortical interneurons](/details-cell/CL4023016) (CSI: 9.38), suggesting a potential, less-characterized function in the central nervous system, possibly related to neuro-immune crosstalk. ## Pathways and Molecular Function The molecular functions and biological pathways associated with [CXCL13](/details-gene/10563) are centered on its identity as a chemokine that signals through G-protein coupled receptors (GPCRs). As an extracellular ligand, it primarily exerts its effects through [chemokine activity](/details-cell/GO:0008009) by binding to and activating the [CXCR5 chemokine receptor](/details-cell/GO:0031724), a mechanism first described in early studies ([Link](https://doi.org/10.1038/35876), [Link](https://doi.org/10.1084/jem.187.4.655)). This interaction is a key event in the Reactome pathway [Chemokine receptors bind chemokines](/details-pathway/R-HSA-380108) and initiates downstream signaling cascades, including [G alpha (i) signalling events](/details-pathway/R-HSA-418594). This primary receptor-ligand interaction drives several critical biological processes. The most prominent is [B cell chemotaxis](/details-cell/GO:0035754), which is essential for guiding B cells into lymphoid follicles. This function is fundamental to [germinal center formation](/details-cell/GO:0002467) and the overall [regulation of humoral immune response](/details-cell/GO:0002920). The high expression of [CXCL13](/details-gene/10563) by [T follicular helper cells](/details-cell/CL0002038) is therefore directly linked to their ability to organize B cell responses. The gene is also implicated in broader processes such as [inflammatory response](/details-cell/GO:0006954) and [chronic inflammatory response](/details-cell/GO:0002544), highlighting its potential role in pathological conditions where ectopic lymphoid structures form. ## Research Directions The established role of [CXCL13](/details-gene/10563) in lymphoid neogenesis and its specific expression pattern opens several avenues for future investigation, particularly concerning its function in pathology and non-canonical contexts. **Proposed Hypotheses:** 1. Given its critical role in [germinal center formation](/details-cell/GO:0002467) and its association with [chronic inflammatory response](/details-cell/GO:0002544), dysregulated expression of [CXCL13](/details-gene/10563) by tissue-resident stromal or immune cells is a key driver for the formation of pathogenic tertiary lymphoid structures in autoimmune diseases and certain cancers. 2. The significant expression of [CXCL13](/details-gene/10563) in [VIP GABAergic cortical interneurons](/details-cell/CL4023016) suggests a novel neuromodulatory function. We hypothesize that neuronal-derived [CXCL13](/details-gene/10563) participates in neuro-immune signaling, potentially recruiting CXCR5-expressing microglia or T cells to specific synaptic regions during inflammation or injury, thereby modulating neuronal function and survival. **Experimental Approach:** To test the second hypothesis regarding the neuromodulatory role of [CXCL13](/details-gene/10563), a multi-step approach could be employed. First, co-expression of [CXCL13](/details-gene/10563) mRNA and VIP protein in the cortex could be validated using spatial transcriptomics or multiplex fluorescence in situ hybridization (FISH) combined with immunohistochemistry. Second, a conditional knockout mouse model (e.g., *Vip-IRES-Cre* x *Cxcl13fl/fl*) could be generated to specifically ablate [CXCL13](/details-gene/10563) production from these interneurons. The functional consequences could then be assessed in a model of neuroinflammation, such as experimental autoimmune encephalomyelitis (EAE) or lipopolysaccharide challenge, by quantifying immune cell infiltration into the brain parenchyma, measuring changes in synaptic activity via electrophysiology, and evaluating behavioral outcomes. **Therapeutic Potential:** [CXCL13](/details-gene/10563) represents a compelling therapeutic target for conditions characterized by pathogenic lymphocyte infiltration and the formation of ectopic lymphoid structures, such as rheumatoid arthritis, lupus, and B-cell lymphomas. As a secreted protein, it is highly accessible to biologic drugs. The therapeutic strategy would focus on **inhibition**, aiming to disrupt the CXCL13-CXCR5 axis. This could be achieved using neutralizing monoclonal antibodies against [CXCL13](/details-gene/10563) or small molecule antagonists targeting its receptor, CXCR5. Such an approach would be expected to block the recruitment of B cells and T follicular helper cells to sites of inflammation, thereby dampening aberrant humoral immune responses.

Genular Protein ID: 1101403243

Symbol: CXL13_HUMAN

Name: C-X-C motif chemokine 13

UniProtKB Accession Codes:

O43927

Database IDs:

ABCD 1 AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CPTAC 1 CPTC 1 CTD 1 ChiTaRS 1 DIP 1 DNASU 1 DisGeNET 1 EMBL 4 Ensembl 2 EvolutionaryTrace 1 ExpressionAtlas 1 GO 32 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 4 PDBsum 4 PRINTS 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 2 RefSeq 2 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9486651

Title: A B-cell-homing chemokine made in lymphoid follicles activates Burkitt's lymphoma receptor-1.

PubMed ID: 9486651

DOI: 10.1038/35876

PubMed ID: 9463416

Title: B cell-attracting chemokine 1, a human CXC chemokine expressed in lymphoid tissues, selectively attracts B lymphocytes via BLR1/CXCR5.

PubMed ID: 9463416

DOI: 10.1084/jem.187.4.655

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: 109
  • Mass: 12664
  • Checksum: 4057FCA8EFF658A8
  • Sequence:
    • MKFISTSLLL MLLVSSLSPV QGVLEVYYTS LRCRCVQESS VFIPRRFIDR IQILPRGNGC 
PRKEIIVWKK NKSIVCVDPQ AEWIQRMMEV LRKRSSSTLP VPVFKRKIP