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Updated: Jun 6, 2026

Rapid and Robust Analysis of Cellular and Molecular Polarization Induced by Chemokine Signaling
Published on: December 12, 2014
DARC and D6: silent partners in chemokine regulation?
Chris A H Hansell1, Catherine E Hurson, Robert J B Nibbs
1Institute for Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University Place, Glasgow, UK.
Abstract:
Chemokine receptors adorn the surface of leukocytes and other cell types ready to translate the extracellular chemokine environment into functional cellular outcomes. However, there are several molecules that, in many respects, look like chemokine receptors, but which do not have the ability to confer chemotactic potential to cell lines. This apparent silence spurred the search for signalling-independent functions and led to the development of new paradigms of chemokine regulation. In this review, we summarise the experimental basis for these ideas focussing on DARC and D6, the most studied members of this group of molecules. We discuss data generated using in vitro systems and genetically deficient mice, include results from observational human studies, and summarise the key findings of recent research. We take a critical look at current models of in vivo function highlighting important gaps in our knowledge and demonstrating that there is still much to find out about these enigmatic molecules.
Insights
This review explores atypical chemokine receptors like DARC and D6, which lack signaling but regulate chemokine activity. Further research is needed to understand their full in vivo functions and significance.
Area of Science:
- Immunology
- Cell Biology
Background:
- Chemokine receptors mediate leukocyte migration.
- Some molecules resemble chemokine receptors but lack chemotactic signaling.
- This suggests alternative roles in chemokine regulation.
Purpose of the Study:
- To review the functions of atypical chemokine receptors.
- To focus on DARC (Duffy Antigen Receptor for Chemokines) and D6.
- To critically evaluate current understanding of their in vivo roles.
Main Methods:
- Literature review of in vitro studies.
- Analysis of data from genetically deficient mouse models.
- Inclusion of results from human observational studies.
Main Results:
- DARC and D6 are key examples of signaling-deficient chemokine-binding molecules.
- Evidence from various models suggests roles beyond chemotaxis.
- Significant knowledge gaps remain regarding their in vivo functions.
Conclusions:
- Atypical chemokine receptors like DARC and D6 represent a distinct class of chemokine regulators.
- Their non-signaling nature necessitates new functional paradigms.
- Further investigation is crucial to elucidate their complex in vivo roles.
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