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

Annalisa Del Prete, Annalisa Del Prete, Laura Martínez-Muñoz, Cristina Mazzon, Lara Toffali, Francesca Sozio, Francesca Sozio, Lorena Za, Daniela Bosisio, Luisa Gazzurelli, Valentina Salvi, Laura Tiberio, Chiara Liberati, Eugenio Scanziani, Annunciata Vecchi, Carlo Laudanna, Mario Mellado, Alberto Mantovani, Alberto Mantovani, Alberto MantovaniSilvano Sozzani, Silvano Sozzani

Research output: Contribution to journalArticle

Abstract

© 2017 by The American Society of Hematology. 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.
Original languageEnglish
Pages (from-to)1223-1234
Number of pages12
JournalBlood
Volume130
Issue number10
DOIs
Publication statusPublished - Sep 7 2017

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