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Published on: December 4, 2020
Analysis of combinatorial chemokine receptor expression dynamics using multi-receptor reporter mice
Laura Medina-Ruiz1, Robin Bartolini1, Gillian J Wilson1
1Chemokine Research Group, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
Abstract:
Inflammatory chemokines and their receptors are central to the development of inflammatory/immune pathologies. The apparent complexity of this system, coupled with lack of appropriate in vivo models, has limited our understanding of how chemokines orchestrate inflammatory responses and has hampered attempts at targeting this system in inflammatory disease. Novel approaches are therefore needed to provide crucial biological, and therapeutic, insights into the chemokine-chemokine receptor family. Here, we report the generation of transgenic multi-chemokine receptor reporter mice in which spectrally distinct fluorescent reporters mark expression of CCRs 1, 2, 3, and 5, key receptors for myeloid cell recruitment in inflammation. Analysis of these animals has allowed us to define, for the first time, individual and combinatorial receptor expression patterns on myeloid cells in resting and inflamed conditions. Our results demonstrate that chemokine receptor expression is highly specific, and more selective than previously anticipated.
Insights
Researchers developed novel reporter mice to track inflammatory chemokine receptors (CCRs 1-5) on myeloid cells. This study reveals specific and selective receptor expression patterns, advancing understanding of inflammatory responses and potential therapies.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- Inflammatory chemokines and receptors are crucial in immune pathologies.
- Understanding chemokine-driven inflammation is limited by complex systems and lack of in vivo models.
- Targeting chemokine pathways for inflammatory diseases requires better biological insights.
Purpose of the Study:
- To develop a novel in vivo model for studying chemokine receptor expression.
- To define individual and combinatorial chemokine receptor expression patterns on myeloid cells.
- To provide insights into the chemokine-chemokine receptor family for therapeutic development.
Main Methods:
- Generation of transgenic multi-chemokine receptor reporter mice.
- Utilized spectrally distinct fluorescent reporters for CCRs 1, 2, 3, and 5.
- Analyzed receptor expression on myeloid cells in resting and inflamed conditions.
Main Results:
- Successfully generated multi-chemokine receptor reporter mice.
- Defined for the first time specific expression patterns of CCRs 1, 2, 3, and 5 on myeloid cells.
- Demonstrated highly specific and selective chemokine receptor expression, contrary to previous assumptions.
Conclusions:
- The novel reporter mice provide a powerful tool for studying chemokine biology.
- Findings clarify chemokine receptor specificity in myeloid cell recruitment during inflammation.
- This work paves the way for improved therapeutic strategies targeting chemokine pathways.
