CCRL2 Expression by Specialized Lung Capillary Endothelial Cells Controls NK-cell Homing in Lung Cancer.

Autor:	Sozio F; Department of Molecular Medicine, Sapienza University of Rome, Laboratory Affiliated to Institute Pasteur-Italia, Rome, Italy., Schioppa T; Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.; IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy., Laffranchi M; Department of Molecular Medicine, Sapienza University of Rome, Laboratory Affiliated to Institute Pasteur-Italia, Rome, Italy., Salvi V; Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy., Tamassia N; Department of Medicine, Section of General Pathology, University of Verona, Italy., Bianchetto-Aguilera FM; Department of Medicine, Section of General Pathology, University of Verona, Italy., Tiberio L; Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy., Bonecchi R; IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy., Bosisio D; Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy., Parmentier M; WELBIO and I.R.I.B.H.M., Université Libre de Bruxelles, Brussels, Belgium., Bottazzi B; IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy., Leone R; IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy., Russo E; Department of Molecular Medicine, Sapienza University of Rome, Laboratory Affiliated to Institute Pasteur-Italia, Rome, Italy., Bernardini G; Department of Molecular Medicine, Sapienza University of Rome, Laboratory Affiliated to Institute Pasteur-Italia, Rome, Italy., Garofalo S; Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy., Limatola C; Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy.; IRCCS Neuromed, Pozzilli (IS), Italy., Gismondi A; Department of Molecular Medicine, Sapienza University of Rome, Laboratory Affiliated to Institute Pasteur-Italia, Rome, Italy., Sciumè G; Department of Molecular Medicine, Sapienza University of Rome, Laboratory Affiliated to Institute Pasteur-Italia, Rome, Italy., Mantovani A; IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.; The William Harvey Research Institute, Queen Mary University of London, London, United Kingdom., Del Prete A; Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.; IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy., Sozzani S; Department of Molecular Medicine, Sapienza University of Rome, Laboratory Affiliated to Institute Pasteur-Italia, Rome, Italy.; IRCCS Neuromed, Pozzilli (IS), Italy.
Jazyk:	angličtina
Zdroj:	Cancer immunology research [Cancer Immunol Res] 2023 Sep 01; Vol. 11 (9), pp. 1280-1295.
DOI:	10.1158/2326-6066.CIR-22-0951
Abstrakt:	Patterns of receptors for chemotactic factors regulate the homing of leukocytes to tissues. Here we report that the CCRL2/chemerin/CMKLR1 axis represents a selective pathway for the homing of natural killer (NK) cells to the lung. C-C motif chemokine receptor-like 2 (CCRL2) is a nonsignaling seven-transmembrane domain receptor able to control lung tumor growth. CCRL2 constitutive or conditional endothelial cell targeted ablation, or deletion of its ligand chemerin, were found to promote tumor progression in a Kras/p53Flox lung cancer cell model. This phenotype was dependent on the reduced recruitment of CD27- CD11b+ mature NK cells. Other chemotactic receptors identified in lung-infiltrating NK cells by single-cell RNA sequencing (scRNA-seq), such as Cxcr3, Cx3cr1, and S1pr5, were found to be dispensable in the regulation of NK-cell infiltration of the lung and lung tumor growth. scRNA-seq identified CCRL2 as the hallmark of general alveolar lung capillary endothelial cells. CCRL2 expression was epigenetically regulated in lung endothelium and it was upregulated by the demethylating agent 5-aza-2'-deoxycytidine (5-Aza). In vivo administration of low doses of 5-Aza induced CCRL2 upregulation, increased recruitment of NK cells, and reduced lung tumor growth. These results identify CCRL2 as an NK-cell lung homing molecule that has the potential to be exploited to promote NK cell-mediated lung immune surveillance. (©2023 American Association for Cancer Research.)
Databáze:	MEDLINE
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