A dynamic spectrum of monocytes arising from the in situ reprogramming of CCR2+ monocytes at a site of sterile injury.
A dynamic spectrum of monocytes arising from the in situ reprogramming of CCR2+ monocytes at a site of sterile injury.
复制标题
DOI：
10.1084/jem.20141539
复制
发表时间：
2015-04-06
期刊：
影响因子：
--
通讯作者：
Kubes P
中科院分区：
文献类型：
--
作者：
Dal-Secco D;Wang J;Zeng Z;Kolaczkowska E;Wong CH;Petri B;Ransohoff RM;Charo IF;Jenne CN;Kubes P
无菌性肝损伤后，CCR 2 hiCX 3CR 1 low炎性单核细胞浸润肝脏并在损伤部位周围形成环状结构。然后细胞转变为进入损伤部位的CCR 2lowCX 3CR 1hi替代单核细胞;这种表型转变是最佳修复所必需的。单核细胞从血液中募集到炎症部位，在那里它们有助于伤口愈合和组织修复。单核细胞至少有两个亚群：经典或促炎（CCR 2 hiCX 3CR 1 low）和非经典、巡逻或替代（CCR 2lowCX 3CR 1hi）单核细胞。使用旋转盘共聚焦活体显微镜和小鼠与荧光报告的每个这些子集，我们能够跟踪的单核细胞进入无菌肝损伤在体内的网站的动态光谱。我们观察到CCR 2 hiCX 3CR 1 low单核细胞在早期被募集并持续至少48 h，在损伤区域周围形成环状结构。这些单核细胞在环状结构内原位从CCR 2 hiCx 3CR 1 low转变为CX 3CR 1hiCCR 2low，然后进入损伤部位。这种表型转换对于最佳修复是必不可少的。这些结果证明了经典的促炎性单核细胞局部细胞因子驱动的重编程为非经典的或替代的单核细胞，以促进适当的伤口愈合。
In response to sterile liver injury, CCR2hiCX3CR1low inflammatory monocytes infiltrate the liver and form a ringlike structure around the injury site. The cells then transition into CCR2lowCX3CR1hi alternative monocytes that enter the injury site; this phenotypic transition was required for optimal repair. Monocytes are recruited from the blood to sites of inflammation, where they contribute to wound healing and tissue repair. There are at least two subsets of monocytes: classical or proinflammatory (CCR2hiCX3CR1low) and nonclassical, patrolling, or alternative (CCR2lowCX3CR1hi) monocytes. Using spinning-disk confocal intravital microscopy and mice with fluorescent reporters for each of these subsets, we were able to track the dynamic spectrum of monocytes that enter a site of sterile hepatic injury in vivo. We observed that the CCR2hiCX3CR1low monocytes were recruited early and persisted for at least 48 h, forming a ringlike structure around the injured area. These monocytes transitioned, in situ, from CCR2hiCx3CR1low to CX3CR1hiCCR2low within the ringlike structure and then entered the injury site. This phenotypic conversion was essential for optimal repair. These results demonstrate a local, cytokine driven reprogramming of classic, proinflammatory monocytes into nonclassical or alternative monocytes to facilitate proper wound-healing.