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Blood. 2017 Sep 7;130(10):1223-1234. doi: 10.1182/blood-2017-04-777680. Epub 2017 Jul 25.

The atypical receptor CCRL2 is required for CXCR2-dependent neutrophil recruitment and tissue damage.

Author information

1
Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
2
Humanitas Clinical and Research Center, Rozzano-Milano, Italy.
3
Department of Immunology and Oncology, Centro Nacional de Biotecnología, Madrid, Spain.
4
Department of Medicine, University of Verona, Verona, Italy.
5
Axxam Discovery Biology, Bresso, Italy.
6
Department of Veterinary Sciences and Public Health, University of Milan, Milan, Italy.
7
Laboratory of Immunology, Humanitas University, Rozzano-Milano, Italy; and.
8
The William Harvey Research Institute, Queen Mary University of London, London, United Kingdom.

Abstract

CCRL2 is a 7-transmembrane domain receptor that shares structural and functional similarities with the family of atypical chemokine receptors (ACKRs). CCRL2 is upregulated by inflammatory signals and, unlike other ACKRs, it is not a chemoattractant-scavenging receptor, does not activate β-arrestins, and is widely expressed by many leukocyte subsets. Therefore, the biological role of CCRL2 in immunity is still unclear. We report that CCRL2-deficient mice have a defect in neutrophil recruitment and are protected in 2 models of inflammatory arthritis. In vitro, CCRL2 was found to constitutively form homodimers and heterodimers with CXCR2, a main neutrophil chemotactic receptor. By heterodimerization, CCRL2 could regulate membrane expression and promote CXCR2 functions, including the activation of β2-integrins. Therefore, upregulation of CCRL2 observed under inflammatory conditions is functional to finely tune CXCR2-mediated neutrophil recruitment at sites of inflammation.

PMID:
28743719
DOI:
10.1182/blood-2017-04-777680
[Indexed for MEDLINE]
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