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.

The atypical receptor CCRL2 is required for CXCR2-dependent neutrophil recruitment and tissue damage / A. Del Prete, L. Martínez-Muñoz, C. Mazzon, L. Toffali, F. Sozio, L. Za, D. Bosisio, L. Gazzurelli, V. Salvi, L. Tiberio, C. Liberati, E. Scanziani, A. Vecchi, C. Laudanna, M. Mellado, A. Mantovani, S. Sozzani. - In: BLOOD. - ISSN 0006-4971. - 130:10(2017), pp. 1223-1234. [10.1182/blood-2017-04-777680]

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

E. Scanziani;A. Vecchi;
2017

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.
animals; arthritis; cd18 antigens; cell survival; disease models, animal; inflammation; mice, knockout; neutrophil infiltration; neutrophils; protein conformation; protein multimerization; receptors, chemokine; receptors, interleukin-8B; signal transduction; biochemistry; immunology; hematology; cell biology
Settore VET/03 - Patologia Generale e Anatomia Patologica Veterinaria
2017
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/554189
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