title: CX3CL1-CX3CR1 Interaction Increases the Population of Ly6C(-)CX3CR1(hi) Macrophages Contributing to Unilateral Ureteral Obstruction-Induced Fibrosis.
abstract: Chemokines modulate inflammatory responses that are prerequisites for kidney injury. The specific role of monocyte-associated CX3CR1 and its cognate ligand CX3CL1 in unilateral ureteral obstruction (UUO)-induced kidney injury remains unclear. In this study, we found that UUO caused a CCR2-dependent increase in numbers of Ly6C(hi) monocytes both in the blood and kidneys and of Ly6C(-)CX3CR1(+) macrophages in the obstructed kidneys of mice. Using CX3CR1(gfp/+) knockin mice, we observed a rapid conversion of infiltrating proinflammatory Ly6C(+)CX3CR1(1o) monocytes/macrophages to anti-inflammatory Ly6C(-)CX3CR1(hi) macrophages. CX3CR1 deficiency affected neither monocyte trafficking nor macrophage differentiation in vivo upon renal obstruction, but CX3CR1 expression in monocytes and macrophages was required for increases in fibrosis in the obstructed kidneys. Mechanistically, CX3CL1-CX3CR1 interaction increases Ly6C(-)CX3CR1(hi) macrophage survival within the obstructed kidneys. Therefore, CX3CL1 and CX3CR1 may represent attractive therapeutic targets in obstructive nephropathy.
authors.affiliation: Beijing Anzhen Hospital, Affiliated to Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China; Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing 100029, China; and Key Laboratory of Molecular Medicine, Second Affiliated Hospital of Nanchang University, Nanchang 330006, China.
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Peng
authors.affiliation: Beijing Anzhen Hospital, Affiliated to Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China; Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing 100029, China; and.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Beijing Anzhen Hospital, Affiliated to Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China; Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing 100029, China; and.
authors.forename: Zhicheng
authors.initials: Z
authors.lastname: Xiao
authors.affiliation: Beijing Anzhen Hospital, Affiliated to Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China; Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing 100029, China; and.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Beijing Anzhen Hospital, Affiliated to Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China; Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing 100029, China; and jdu@bcm.edu.
authors.forename: Jie
authors.initials: J
authors.lastname: Du
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D000073883:CX3C Chemokine Receptor 1; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D054428:Chemokine CX3CL1 / Q000378:metabolism*; D005355:Fibrosis / Q000276:immunology / Q000473:pathology*; D007668:Kidney / Q000293:injuries / Q000473:pathology; D007674:Kidney Diseases / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D054390:Receptors, CCR2 / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D014517:Ureteral Obstruction / Q000276:immunology / Q000473:pathology*
chemical_list: D000950:Antigens, Ly; D000073883:CX3C Chemokine Receptor 1; C515335:Ccr2 protein, mouse; D054428:Chemokine CX3CL1; C515539:Cx3cl1 protein, mouse; C471885:Cx3cr1 protein, mouse; C494192:Ly-6C antigen, mouse; D054390:Receptors, CCR2; D019707:Receptors, Chemokine