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A Flow Cytometry-based Assay to Identify Compounds That Disrupt Binding of Fluorescently-labeled CXC Chemokine Ligand 12 to CXC Chemokine Receptor 4
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A Flow Cytometry-based Assay to Identify Compounds That Disrupt Binding of Fluorescently-labeled CXC Chemokine Ligand 12 to CXC Chemokine Receptor 4

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Pathological roles of the homeostatic chemokine CXCL12

Rik Janssens1, Sofie Struyf1, Paul Proost1

  • 1KU Leuven, University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Molecular Immunology, B-3000 Leuven, Belgium.

Cytokine & Growth Factor Reviews
|November 7, 2018
PubMed

Insights

The CXCL12/CXCR4/ACKR3 axis plays a dual role in health and disease. While crucial for normal body functions, its dysregulation contributes to various pathologies, but targeting this axis can offer therapeutic benefits.

Area of Science:

  • Immunology
  • Molecular Biology
  • Pathology

Background:

  • Chemokine CXCL12 (CXCL12) is traditionally viewed as a homeostatic chemokine vital for embryogenesis, hematopoiesis, and angiogenesis.
  • Aberrant CXCL12 expression, including specific splicing variants, and its receptors CXC chemokine receptor 4 (CXCR4) and atypical chemokine receptor 3 (ACKR3), are implicated in various diseases.
  • Posttranslational modifications of CXCL12 during disease further complicate its role by altering its activity.

Purpose of the Study:

  • To review the multifaceted role of the CXCL12/CXCR4/ACKR3 signaling axis in prevalent human pathologies.
  • To explore the therapeutic potential of targeting this axis in disease treatment and prevention.

Main Methods:

  • Literature review of studies investigating the CXCL12/CXCR4/ACKR3 axis in various diseases.
  • Analysis of therapeutic strategies involving CXCL12-neutralizing antibodies and antagonists of CXCR4 or ACKR3.

Main Results:

  • The CXCL12/CXCR4/ACKR3 axis is involved in numerous pathologies, including cancer, viral infections, inflammatory and autoimmune diseases, and neurological disorders.
  • Targeting this axis with neutralizing antibodies or small-molecule antagonists has shown promise in delaying disease onset or progression in several conditions.
  • Conversely, CXCL12 exhibits protective roles in neurodegenerative diseases like Alzheimer's and multiple sclerosis, and aids in wound healing.

Conclusions:

  • The CXCL12/CXCR4/ACKR3 axis presents a complex dichotomy, acting as both a driver of pathology and a mediator of protective functions.
  • Targeting this axis offers a promising therapeutic avenue for a range of diseases, though its beneficial roles in certain conditions must also be considered.

Keywords:
ACKR3CXCL12CXCR4ChemokineStromal cell-derived factorleukocyte migration

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