GO:0016494 C-X-C chemokine receptor activity: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0016494 (C-X-C chemokine receptor activity) is a molecular function defined as the binding of a C-X-C chemokine and transmission of a signal across the membrane to initiate a change in cell activity.
• C-X-C chemokines are distinguished by a single amino acid separating the first two cysteines of the conserved four-cysteine motif, which dictates receptor selectivity.
• Receptors carrying this activity include CXCR1, CXCR2, CXCR3, CXCR4, CXCR5, CXCR6, and the atypical receptor ACKR3, which collectively govern leukocyte trafficking, inflammation, and tissue homeostasis.
• The CXCR6/CXCL16 axis is directly implicated in autoimmune disease pathogenesis and in prostate cancer progression, where receptor expression correlates with clinical outcome.
• C-X-C chemokine receptor signaling is modulated by heterologous receptor systems such as HCAR2 in microglia and by adenosine A2A receptor signaling in CD8+ T cells, revealing layers of cross-talk.
• CRISPR-based knockout, knock-in, and overexpression models are essential for dissecting which C-X-C chemokine receptor genes causally drive disease phenotypes.
Description
C-X-C chemokine receptor activity (GO:0016494) is a molecular function that couples extracellular C-X-C chemokine binding to intracellular signal transduction, thereby converting a chemical gradient into directed cell behavior. This activity is central to immunology because it controls the recruitment, retention, and activation of leukocytes during inflammation, infection, and tissue repair. The defining structural feature of the C-X-C chemokine family is a single amino acid inserted between the first two cysteines of the characteristic four-cysteine motif, a spacing that determines which receptors are engaged and how strongly. Researchers study GO:0016494 because dysregulated C-X-C chemokine receptor signaling underpins a broad spectrum of human diseases, including autoimmune disorders, cancer, and neuroinflammatory conditions. For example, the CXCR6/CXCL16 axis has been linked to autoimmune disease pathology, and CXCR6 expression in prostate cancer is associated with prognostic significance. In parallel, C-X-C chemokine induction following endotoxemia drives neutrophil sequestration, illustrating how this activity translates directly into acute inflammatory responses. Because these receptors sit at the interface between the extracellular chemokine milieu and intracellular signaling networks, they are attractive targets for both mechanistic studies and therapeutic intervention. Understanding GO:0016494 therefore requires integrating receptor pharmacology, cell biology, and disease models, with CRISPR-based genetic tools providing the causal evidence that observational studies cannot.
C-X-C chemokine receptor activity At A Glance
| GO ID | GO:0016494 |
|---|---|
| GO term | C-X-C chemokine receptor activity |
| Ontology | molecular_function |
| Synonym | None listed in QuickGO |
| Major function | Binding a C-X-C chemokine and transmitting a signal across the membrane to initiate a change in cell activity |
| Defining ligand feature | Single amino acid between the first two cysteines of the four-cysteine motif |
| Representative receptors | CXCR1, CXCR2, CXCR3, CXCR4, CXCR5, CXCR6, ACKR3 |
| Associated processes | Leukocyte trafficking, inflammation, neutrophil sequestration, immune cell polarization |
| Disease relevance | Autoimmune disease, prostate cancer, colorectal cancer chemoresistance, neuroinflammation |
What Is GO:0016494?
In plain terms, GO:0016494 describes what happens when a C-X-C chemokine docks onto its receptor and the receptor relays that message across the cell membrane. The QuickGO definition states that this activity combines with a C-X-C chemokine and transmits the signal from one side of the membrane to the other to initiate a change in cell activity. A C-X-C chemokine is defined by a single amino acid between the first two cysteines of the characteristic four-cysteine motif. This molecular function is therefore both a binding event and a signaling event: it is not merely chemokine sequestration but active transmembrane information transfer.
Why Is C-X-C chemokine receptor activity Important in Cell Biology?
GO:0016494 matters because C-X-C chemokine receptors are the principal sensors that convert chemokine gradients into directed immune cell migration and activation, making them central to host defense and to the pathogenesis of inflammatory and malignant diseases. Experimental evidence shows that C-X-C chemokine induction after endotoxemia drives neutrophil sequestration in vivo, directly linking this molecular activity to acute tissue inflammation. In cancer, CXCR6 expression in prostate tumors carries prognostic significance, and tumor-associated macrophage signaling through chemokine axes can confer 5-fluorouracil resistance in colorectal cancer. In the nervous system, cross-talk between HCAR2 and CXCR1 in microglia suggests that C-X-C chemokine receptor activity participates in neuroinflammatory pathophysiology. Because these receptors are druggable and genetically tractable, they remain high-priority targets for both basic and translational research.
• Controls directed leukocyte migration and positioning during inflammation and immune surveillance.
• Mediates neutrophil sequestration following endotoxemia, a model of acute systemic inflammation.
• The CXCR6/CXCL16 axis is implicated in autoimmune disease pathogenesis.
• CXCR6 expression has prognostic significance in prostate cancer.
• Chemokine receptor signaling in tumor-associated macrophages contributes to colorectal cancer 5-fluorouracil resistance.
• C-X-C chemokine receptor activity is subject to cross-talk with other G-protein-coupled receptors such as HCAR2 in microglia.
• Adenosine A2A receptor signaling regulates C-X-C chemokine receptor expression in CD8+ T cells in a neurodevelopmental disease model.
• Receptor-ligand specificity is dictated by the C-X-C motif spacing, making these receptors selectively targetable.
• Provides mechanistic entry points for anti-inflammatory and immuno-oncology therapeutic strategies.
• Enables CRISPR-based causal testing of receptor gene function in disease models.
Molecular Mechanism of C-X-C chemokine receptor activity
Chemokine recognition and binding selectivity
In simple terms: The receptor first has to recognize and grab the right chemokine.
C-X-C chemokine receptor activity begins with selective recognition of a C-X-C chemokine ligand. The C-X-C subclass is defined by a single amino acid between the first two cysteines of the characteristic four-cysteine motif, and this structural feature is a key determinant of receptor-ligand specificity. Structure-activity studies of chemokines established that the conserved cysteine framework and the residues surrounding it govern receptor engagement and biological potency. This binding step is the molecular basis for why C-X-C chemokines act on distinct receptor subsets rather than promiscuously across all chemokine receptors.
Transmembrane signal transmission
In simple terms: Once the chemokine is bound, the receptor passes the message across the membrane.
The defining event of GO:0016494 is transmission of the signal from one side of the membrane to the other to initiate a change in cell activity. This transmembrane relay converts extracellular chemokine occupancy into intracellular biochemical changes. In vivo, C-X-C chemokine induction is functionally coupled to downstream cellular responses such as neutrophil sequestration, demonstrating that receptor engagement produces measurable physiological signaling output. The activity is therefore not passive binding but an active information transfer step.
Integration with heterologous receptor systems
In simple terms: Other receptors can influence how C-X-C chemokine receptors behave.
C-X-C chemokine receptor activity does not operate in isolation. In microglia, pathophysiological studies have proposed cross-talk between HCAR2 and CXCR1, indicating that the functional output of C-X-C chemokine receptor signaling can be modulated by co-expressed G-protein-coupled receptors. Similarly, in CD8+ T cells from a BTBR autism model, adenosine A2A receptor signaling is associated with regulation of C-C and C-X-C chemokine receptor expression, showing that neuromodulatory receptor pathways can reshape chemokine receptor profiles. These findings support a model in which the effective signaling capacity of GO:0016494 is context-dependent.
Downstream cellular outcomes
In simple terms: The signal ultimately changes what the cell does.
The functional consequence of C-X-C chemokine receptor activity is a change in cell behavior, which in immune cells typically means directed migration, retention, or altered activation state. In disease contexts, this activity contributes to pathological outcomes: CXCR6/CXCL16 signaling is linked to autoimmune disease processes, and CXCR6 expression in prostate cancer is associated with prognostic significance. In colorectal cancer, chemokine-driven signaling in tumor-associated macrophages promotes MRP1 membrane translocation and 5-fluorouracil resistance, illustrating how receptor activity can shape therapeutic response. These examples show that GO:0016494 is mechanistically connected to clinically meaningful cellular phenotypes.
Regulation by inflammatory mediators
In simple terms: Inflammation can turn C-X-C chemokine signaling up or down.
C-X-C chemokine receptor activity is regulated at the level of ligand availability and receptor expression by inflammatory mediators. IL-1 regulates in vivo C-X-C chemokine induction and neutrophil sequestration following endotoxemia, providing direct evidence that upstream cytokines control the chemokine arm of this signaling system. In parallel, TREM2 promotes macrophage polarization from M1 to M2 and suppresses osteoarthritis through the NF-kB/CXCL3 axis, indicating that C-X-C chemokine ligands are embedded in broader polarization and inflammatory circuits. Together, these studies show that the activity of GO:0016494 is tuned by the surrounding cytokine and inflammatory environment.
Key Genes Involved in GO:0016494 C-X-C chemokine receptor activity
The following genes encode receptors, ligands, and regulatory proteins that are experimentally and clinically connected to C-X-C chemokine receptor activity (GO:0016494).
| Gene | Major Role | Research Relevance |
|---|---|---|
| CXCR1 | C-X-C chemokine receptor; proposed cross-talk with HCAR2 in microglia | Microglial pathophysiology and neuroinflammation studies |
| CXCR6 | Receptor for CXCL16; mediates inflammatory cell recruitment | Autoimmune disease and prostate cancer prognosis |
| CXCL16 | C-X-C chemokine ligand for CXCR6 | Prostate cancer prognostic marker and autoimmune axis |
| CXCL3 | C-X-C chemokine ligand downstream of TREM2/NF-kB | Macrophage polarization and osteoarthritis |
| CXCL17 | Chemokine ligand in tumor-associated macrophage signaling | Colorectal cancer 5-fluorouracil resistance |
| CXCL22 | Chemokine ligand in tumor-associated macrophage signaling | Colorectal cancer chemoresistance |
| CCR4 | Chemokine receptor cooperating in the CXCL17/CXCL22 axis | Colorectal cancer drug resistance |
| ATF6 | Stress-responsive transcription factor in the chemokine resistance axis | Colorectal cancer chemoresistance |
| GRP78 | ER chaperone in the chemokine-driven resistance pathway | Colorectal cancer chemoresistance |
| MRP1 | Drug efflux transporter whose membrane translocation is chemokine-driven | Colorectal cancer 5-fluorouracil resistance |
| TREM2 | Macrophage polarization regulator upstream of CXCL3 | Osteoarthritis and macrophage biology |
| NF-kB | Transcription factor controlling CXCL3 expression | Osteoarthritis inflammation |
| HCAR2 | G-protein-coupled receptor showing cross-talk with CXCR1 | Microglia pathophysiology |
| Adenosine A2A receptor | Neuromodulatory receptor regulating chemokine receptor expression | CD8+ T cell regulation in autism model |
| IL-1 | Cytokine regulating in vivo C-X-C chemokine induction | Endotoxemia and neutrophil sequestration |
| CXCL1/CXCL2 family ligands | C-X-C chemokines driving neutrophil recruitment | Endotoxemia and acute inflammation |
| Chemokine cysteine motif determinants | Structural features governing receptor selectivity | Structure-activity relationship studies |
How Is C-X-C chemokine receptor activity Regulated?
C-X-C chemokine receptor activity is regulated at multiple levels. Upstream, inflammatory cytokines such as IL-1 control in vivo C-X-C chemokine induction and subsequent neutrophil sequestration, demonstrating cytokine-dependent regulation of the ligand arm of this activity. At the receptor level, heterologous G-protein-coupled receptor systems can modulate C-X-C chemokine receptor function; for example, HCAR2 has been proposed to cross-talk with CXCR1 in microglia. In T cells, adenosine A2A receptor signaling is associated with regulation of C-C and C-X-C chemokine receptor expression, indicating neuromodulatory control of receptor profiles. Downstream, transcription factors such as NF-kB regulate C-X-C chemokine ligand expression, as shown for CXCL3 in macrophage polarization. Finally, the structural determinants of the C-X-C motif itself impose intrinsic selectivity constraints on which ligand-receptor pairs can productively signal.
C-X-C chemokine receptor activity and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| CXCR6 | Autoimmune disease; prostate cancer prognosis | CXCR6 knockout and knock-in cell lines; autoimmune and prostate cancer models |
| CXCL16 | Autoimmune disease; prostate cancer | CXCL16 overexpression and knockout models |
| CXCL17/CXCL22-CCR4 axis | Colorectal cancer 5-fluorouracil resistance | Tumor-associated macrophage co-culture with colorectal cancer cells; knockout of axis components |
| TREM2/NF-kB/CXCL3 | Osteoarthritis; macrophage polarization | TREM2 knockout and overexpression macrophage models; osteoarthritis models |
| HCAR2/CXCR1 | Microglial neuroinflammation | Microglial cell lines with CXCR1 knockout or HCAR2 modulation |
Autoimmune disease and the CXCR6/CXCL16 axis
The CXCR6/CXCL16 axis has been reviewed as a significant contributor to autoimmune disease pathogenesis, linking C-X-C chemokine receptor activity to chronic inflammatory tissue damage. Because CXCR6 is a receptor for the C-X-C chemokine CXCL16, this axis is a direct example of GO:0016494 in human disease. Experimental models that manipulate CXCR6 or CXCL16 expression are therefore valuable for testing causality in autoimmune contexts.
Cancer progression and chemoresistance
CXCR6 expression has prognostic significance in prostate cancer, where the receptor and its ligand CXCL16 are associated with clinical outcome. In colorectal cancer, tumor-associated macrophages confer 5-fluorouracil resistance by promoting MRP1 membrane translocation via an intercellular CXCL17/CXCL22-CCR4-ATF6-GRP78 axis, demonstrating that chemokine signaling can directly alter drug sensitivity. These findings position C-X-C chemokine receptor activity as a modifier of both tumor progression and therapeutic response.
Neuroinflammation and neurodevelopmental conditions
In microglia, proposed cross-talk between HCAR2 and CXCR1 suggests that C-X-C chemokine receptor activity participates in neuroinflammatory pathophysiology. In a BTBR autism mouse model, immune alterations in CD8+ T cells are associated with neuronal C-C and C-X-C chemokine receptor regulation through adenosine A2A receptor signaling, linking chemokine receptor biology to neurodevelopmental immune dysregulation. These studies indicate that GO:0016494 is relevant beyond classical peripheral inflammation.
Osteoarthritis and macrophage polarization
TREM2 promotes macrophage polarization from M1 to M2 and suppresses osteoarthritis through the NF-kB/CXCL3 axis, placing a C-X-C chemokine ligand downstream of a key macrophage regulatory pathway. This connects C-X-C chemokine biology to joint degeneration and suggests that modulating this axis could influence osteoarthritis progression.
From C-X-C chemokine receptor activity-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Is CXCR6 required for autoimmune tissue damage? | CXCR6 knockout cell lines and in vivo autoimmune models |
| Does CXCR6 expression level affect prostate cancer prognosis? | CXCR6 knock-in reporter or overexpression models in prostate cancer cells |
| Does the CXCL17/CXCL22-CCR4 axis causally drive 5-fluorouracil resistance? | Knockout of CXCL17, CXCL22, or CCR4 in tumor-associated macrophage and colorectal cancer co-culture systems |
| Does TREM2 suppress osteoarthritis via CXCL3? | TREM2 knockout and overexpression macrophage models with CXCL3 readouts |
| Does HCAR2 cross-talk with CXCR1 in microglia? | CXCR1 knockout or tagged knock-in microglial cells with HCAR2 modulation |
| Does adenosine A2A receptor signaling regulate C-X-C chemokine receptor expression? | A2A receptor knockout or overexpression T cell models |
How to Study the C-X-C chemokine receptor activity Process
| Method | What It Measures | Typical Application |
|---|---|---|
| CRISPR knockout | Loss of receptor gene function | Testing requirement of CXCR6 or CXCR1 in disease models |
| CRISPR knock-in | Tagged or mutant receptor expression | Tracking receptor localization and signaling |
| Overexpression | Gain of receptor or ligand function | Testing sufficiency of CXCL16 or CXCL3 in disease phenotypes |
| RNA-seq | Transcriptional changes in chemokine receptors and ligands | Mapping regulatory networks such as A2A receptor effects on chemokine receptor expression |
| Neutrophil sequestration assay | In vivo neutrophil recruitment | Measuring C-X-C chemokine induction after endotoxemia |
| Macrophage polarization assay | M1 versus M2 marker expression | Evaluating TREM2/NF-kB/CXCL3 effects in osteoarthritis |
| Tumor-macrophage co-culture | Drug resistance and efflux transporter localization | Studying CXCL17/CXCL22-CCR4-driven 5-fluorouracil resistance |
| Structure-activity analysis | Ligand-receptor binding determinants | Defining C-X-C chemokine specificity |
Genetic perturbation with CRISPR
CRISPR knockout, knock-in, and overexpression models allow causal testing of whether a specific C-X-C chemokine receptor gene is required for a phenotype. For example, knocking out CXCR6 or its ligand CXCL16 can test the axis in autoimmune and prostate cancer models. Similarly, perturbing components of the CXCL17/CXCL22-CCR4-ATF6-GRP78 axis can establish whether chemokine signaling causally drives 5-fluorouracil resistance.
Expression profiling and transcriptomics
RNA-seq and targeted expression profiling can quantify C-X-C chemokine receptor and ligand transcripts across conditions. Studies of adenosine A2A receptor signaling in CD8+ T cells used expression analysis to associate receptor regulation with immune alterations, illustrating how transcriptomics can reveal regulatory relationships. In osteoarthritis models, expression of CXCL3 downstream of TREM2 and NF-kB can be profiled to map the signaling axis.
Functional immune and inflammatory assays
Neutrophil sequestration assays following endotoxemia provide a functional readout of C-X-C chemokine induction and receptor activity in vivo. Macrophage polarization assays can measure M1-to-M2 transitions downstream of TREM2 and CXCL3. Co-culture systems between tumor-associated macrophages and cancer cells can quantify drug resistance phenotypes driven by chemokine axes.
Structure-activity and ligand-receptor specificity studies
Structure-activity relationship studies of chemokines have defined how the conserved cysteine motif and flanking residues determine receptor engagement. These approaches help assign specific ligand-receptor pairs to GO:0016494 and predict which C-X-C chemokines will activate a given receptor.
How CRISPR Can Be Used to Study GO:0016494 C-X-C chemokine receptor activity
Knockout
CRISPR knockout of C-X-C chemokine receptor genes such as CXCR6 or CXCR1 enables loss-of-function tests of their role in autoimmune, cancer, and neuroinflammatory phenotypes. Knockout of ligand genes such as CXCL16 or CXCL3 can similarly test the ligand arm of the axis. These models are essential for distinguishing correlation from causation in chemokine biology.
Point Mutation
Point mutations can be introduced to dissect specific residues that determine ligand binding or signaling selectivity within the C-X-C chemokine receptor. Because the C-X-C motif spacing is a key specificity determinant, targeted mutation of receptor or ligand residues can reveal which structural features are required for productive signaling. Such models complement broader knockout approaches by preserving receptor expression while altering function.
Knock-in
Knock-in of tagged or reporter versions of C-X-C chemokine receptors allows tracking of receptor expression, localization, and trafficking in live or fixed cells. This is particularly useful for studying receptors such as CXCR6 in prostate cancer models where expression level has prognostic significance. Knock-in strategies can also introduce disease-associated variants to test their functional impact.
Overexpression
Overexpression of C-X-C chemokine receptors or their ligands tests whether increased signaling is sufficient to drive a phenotype. For example, overexpression of CXCL3 downstream of TREM2 can probe macrophage polarization and osteoarthritis-related outcomes. Overexpression of CXCL16 or CXCR6 can test sufficiency in prostate cancer and autoimmune models.
How EDITGENE Supports C-X-C chemokine receptor activity Research
Researchers studying C-X-C chemokine receptor activity-related genes often need to determine whether a candidate gene is causally involved in a disease phenotype or merely correlated with it. Observational expression data, such as the prognostic association of CXCR6 in prostate cancer, cannot by itself establish causality. CRISPR-based genetic models provide the controlled perturbations needed to move from association to mechanism, whether the question concerns autoimmune disease, cancer chemoresistance, or neuroinflammation.
Contact EDITGENE today to design your custom CRISPR model for C-X-C chemokine receptor activity research.
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CXCR2 Knockout HEK293 Cell Line | EDJ-KQ271 | Human | 3579 | Details Get a Quote |
| CXCR4 Knockout HEK293 Cell Line | EDJ-KQ1608 | Human | 7852 | Details Get a Quote |
| CXCR1 Knockout HEK293 Cell Line | EDJ-KQ1723 | Human | 3577 | Details Get a Quote |
| ACKR3 Knockout HEK293 Cell Line | EDJ-KQ2468 | Human | 57007 | Details Get a Quote |
| CXCR3 Knockout HEK293 Cell Line | EDJ-KQ4764 | Human | 2833 | Details Get a Quote |
| GPR25 Knockout HEK293 Cell Line | EDJ-KQ4766 | Human | 2848 | Details Get a Quote |
| GPR35 Knockout HEK293 Cell Line | EDJ-KQ4771 | Human | 2859 | Details Get a Quote |
| CXCR6 Knockout HEK293 Cell Line | EDJ-KQ7123 | Human | 10663 | Details Get a Quote |
| CXCR4 Knockout U2OS Cell Line | EDJ-KQ18082 | Human | 7852 | Details Get a Quote |
| CXCR4 Knockout HeLa Cell Line | EDJ-KQ19944 | Human | 7852 | Details Get a Quote |
| ACKR3 Knockout A-549 Cell Line | EDJ-KQ23021 | Human | 57007 | Details Get a Quote |
| ACKR3 Knockout HeLa Cell Line | EDJ-KQ23022 | Human | 57007 | Details Get a Quote |
| CXCR4 Knockout A-549 Cell Line | EDJ-KQ26289 | Human | 7852 | Details Get a Quote |
| GPR35 Knockout A-549 Cell Line | EDJ-KQ27526 | Human | 2859 | Details Get a Quote |
| GPR35 Knockout HCT 116 Cell Line | EDJ-KQ27527 | Human | 2859 | Details Get a Quote |
- 1
- 2
- Next Page »
Frequently Asked Questions About C-X-C chemokine receptor activity
What is GO:0016494?
GO:0016494 is the Gene Ontology molecular function term for C-X-C chemokine receptor activity, defined as combining with a C-X-C chemokine and transmitting the signal from one side of the membrane to the other to initiate a change in cell activity.
What is C-X-C chemokine receptor activity?
It is the activity by which a receptor binds a C-X-C chemokine and relays that signal across the membrane, where a C-X-C chemokine has a single amino acid between the first two cysteines of the four-cysteine motif.
What genes are involved in C-X-C chemokine receptor activity?
Genes encoding C-X-C chemokine receptors and their ligands include CXCR1, CXCR6, CXCL16, CXCL3, CXCL17, and CXCL22, along with cooperating receptors such as CCR4.
Which diseases are linked to C-X-C chemokine receptor activity?
Published work links this activity to autoimmune disease, prostate cancer prognosis, colorectal cancer 5-fluorouracil resistance, osteoarthritis, and neuroinflammation.
How is C-X-C chemokine receptor activity regulated?
It is regulated by inflammatory cytokines such as IL-1, by heterologous receptors such as HCAR2 and adenosine A2A receptor, and by transcription factors such as NF-kB.
What is the role of CXCR6 in disease?
CXCR6 and its ligand CXCL16 are implicated in autoimmune disease pathogenesis and in prostate cancer, where CXCR6 expression has prognostic significance.
How do C-X-C chemokines differ from C-C chemokines?
C-X-C chemokines have a single amino acid between the first two cysteines of the four-cysteine motif, a spacing that distinguishes them from C-C chemokines and influences receptor selectivity.
Can CRISPR be used to study C-X-C chemokine receptor activity?
Yes, CRISPR knockout, knock-in, point mutation, and overexpression models allow causal testing of receptor and ligand genes in disease-relevant systems.
What experimental models are used for C-X-C chemokine receptor research?
Common models include knockout and overexpression cell lines, macrophage polarization assays, neutrophil sequestration assays, and tumor-macrophage co-culture systems.
Why is C-X-C chemokine receptor activity important in cancer?
CXCR6 expression is prognostically significant in prostate cancer, and chemokine signaling in tumor-associated macrophages can drive 5-fluorouracil resistance in colorectal cancer.
Conclusion
C-X-C chemokine receptor activity (GO:0016494) is a molecular function that converts C-X-C chemokine binding into transmembrane signaling and ultimately into changes in cell behavior. Its importance spans autoimmune disease, cancer, osteoarthritis, and neuroinflammation, with specific axes such as CXCR6/CXCL16 and CXCL17/CXCL22-CCR4-ATF6-GRP78 providing mechanistic links to human pathology. Because these receptors and ligands are genetically tractable, CRISPR-based knockout, knock-in, point mutation, and overexpression models are central to establishing causality and to identifying new therapeutic opportunities.
References
- 1. Fang C et al.. 2024. TREM2 promotes macrophage polarization from M1 to M2 and suppresses osteoarthritis through the NF-κB/CXCL3 axis.. Int J Biol Sci 20(6):1992-2007 PMID: 38617547
- 2. Perrone M et al.. 2023. Potential role of the hydroxyl carboxylic acid receptor type 2 (HCAR2) in microglia pathophysiology: A possible cross-talk with C-X-C chemokine receptor 1 (CXCR1).. Neuropharmacology 228:109456 PMID: 36796675
- 3. Bao N et al.. 2023. Role of the CXCR6/CXCL16 axis in autoimmune diseases.. Int Immunopharmacol 121:110530 PMID: 37348231
- 4. Ahmad SF et al.. 2018. Immune Alterations in CD8(+) T Cells Are Associated with Neuronal C-C and C-X-C Chemokine Receptor Regulation Through Adenosine A2A Receptor Signaling in a BTBR T(+) Itpr3(tf)/J Autistic Mouse Model.. Mol Neurobiol 55(3):2603-2616 PMID: 28421534
- 5. Zhang L et al.. 2023. Tumor-associated macrophages confer colorectal cancer 5-fluorouracil resistance by promoting MRP1 membrane translocation via an intercellular CXCL17/CXCL22-CCR4-ATF6-GRP78 axis.. Cell Death Dis 14(9):582 PMID: 37658050
- 6. Richardsen E et al.. 2015. The prognostic significance of CXCL16 and its receptor C-X-C chemokine receptor 6 in prostate cancer.. Am J Pathol 185(10):2722-30 PMID: 26272362
- 7. Clark-Lewis I et al.. 1995. Structure-activity relationships of chemokines.. J Leukoc Biol 57(5):703-11 PMID: 7759949
- 8. Calkins CM et al.. 2002. IL-1 regulates in vivo C-X-C chemokine induction and neutrophil sequestration following endotoxemia.. J Endotoxin Res 8(1):59-67 PMID: 11981446
