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 chemoattractantscavenging receptor, does not activate b-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 b2-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 / DEL PRETE, Annalisa; Martãnez muã±oz, Laura; Mazzon, Cristina; Toffali, Lara; Sozio, Francesca; Za, Lorena; Bosisio, Daniela; Gazzurelli, Luisa; Salvi, Valentina; Tiberio, Laura; Liberati, Chiara; Scanziani, Eugenio; Vecchi, Annunciata; Laudanna, Carlo; Mellado, Mario; Mantovani, Alberto; Sozzani, Silvano. - 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
SOZIO, Francesca;SOZZANI, Silvano
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 chemoattractantscavenging receptor, does not activate b-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 b2-integrins. Therefore, upregulation of CCRL2 observed under inflammatory conditions is functional to finely tune CXCR2-mediated neutrophil recruitment at sites of inflammation.File | Dimensione | Formato | |
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