The atypical receptor CCRL2 is required for CXCR2-dependent neutrophil recruitment and tissue damage.
1223 - 1234
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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.
AuthorsDel Prete, A; Martínez-Muñoz, L; Mazzon, C; Toffali, L; Sozio, F; Za, L; Bosisio, D; Gazzurelli, L; Salvi, V; Tiberio, L; Liberati, C; Scanziani, E; Vecchi, A; Laudanna, C; Mellado, M; Mantovani, A; Sozzani, S
- Inflammation