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.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81430050, 31090363, 81230006, 81100144, 81130001]; Chinese Ministry of Science and TechnologyMinistry of Science and Technology, China [2012CB945104]; Beijing Collaborative Innovative Research Center for Cardiovascular Diseases [PXM2013_014226_07_000088]
第一作者机构：[1]Capital Med Univ, Beijing Anzhen Hosp, Beijing Inst Heart Lung & Blood Vessel Dis, Beijing 100029, Peoples R China;[2]Minist Educ, Key Lab Remodeling Related Cardiovasc Dis, Beijing 100029, Peoples R China;[3]Nanchang Univ, Affiliated Hosp 2, Key Lab Mol Med, Nanchang 330006, Peoples R China;
通讯作者：
通讯机构：[1]Capital Med Univ, Beijing Anzhen Hosp, Beijing Inst Heart Lung & Blood Vessel Dis, Beijing 100029, Peoples R China;[2]Minist Educ, Key Lab Remodeling Related Cardiovasc Dis, Beijing 100029, Peoples R China;[4]Capital Med Univ, Beijing Anzhen Hosp, 2 Anzhen Rd, Beijing 100029, Peoples R China
推荐引用方式(GB/T 7714)：
Peng Xiaogang,Zhang Jing,Xiao Zhicheng,et al.CX3CL1-CX3CR1 Interaction Increases the Population of Ly6C(-) CX3CR1(hi) Macrophages Contributing to Unilateral Ureteral Obstruction-Induced Fibrosis[J].JOURNAL OF IMMUNOLOGY.2015,195(6):2797-2805.doi:10.4049/jimmunol.1403209.
APA：
Peng, Xiaogang,Zhang, Jing,Xiao, Zhicheng,Dong, Yanjun&Du, Jie.(2015).CX3CL1-CX3CR1 Interaction Increases the Population of Ly6C(-) CX3CR1(hi) Macrophages Contributing to Unilateral Ureteral Obstruction-Induced Fibrosis.JOURNAL OF IMMUNOLOGY,195,(6)
MLA：
Peng, Xiaogang,et al."CX3CL1-CX3CR1 Interaction Increases the Population of Ly6C(-) CX3CR1(hi) Macrophages Contributing to Unilateral Ureteral Obstruction-Induced Fibrosis".JOURNAL OF IMMUNOLOGY 195..6(2015):2797-2805
医学