eLife (Jun 2022)

Analysis of combinatorial chemokine receptor expression dynamics using multi-receptor reporter mice

  • Laura Medina-Ruiz,
  • Robin Bartolini,
  • Gillian J Wilson,
  • Douglas P Dyer,
  • Francesca Vidler,
  • Catherine E Hughes,
  • Fabian Schuette,
  • Samantha Love,
  • Marieke Pingen,
  • Alan James Hayes,
  • Jun Fu,
  • Adrian Francis Stewart,
  • Gerard J Graham

DOI
https://doi.org/10.7554/eLife.72418
Journal volume & issue
Vol. 11

Abstract

Read online

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.

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