Laboratory of Innate Immunology, Centre de recherche du CHU de Québec-Université Laval, Québec, QC G1V 4G2, Canada.
Centre de recherche du CHU de Québec, Université Laval, Québec, QC G1V 4G2, Canada.
Cell Rep. 2017 Aug 22;20(8):1830-1843. doi: 10.1016/j.celrep.2017.08.009.
The signals that regulate the fate of circulating monocytes remain unknown. In the present study, we demonstrate that triggering of the NOD2 receptor by muramyl dipeptide (MDP) converts inflammatory Ly6C monocytes into patrolling Ly6C monocytes. Administration of MDP to Nr4a1 mice, which lack Ly6C monocytes, or to Ly6C-depleted mice led to the emergence of blood-patrolling monocytes with a profile similar to that of Ly6C monocytes, including high expression of CX3CR1 and LFA1. Using intravital microscopy in animal models of inflammatory diseases, we also found that converted Ly6C monocytes patrol the endothelium of blood vessels and that their presence contributes to a reduction in the inflammatory response following MDP injection. Our results demonstrate that NOD2 contributes to the regulation of blood monocytes and suggest that it could be therapeutically targeted to treat inflammatory diseases.
目前尚不清楚调节循环单核细胞命运的信号。在本研究中，我们证明了 NOD2 受体被 muramyl dipeptide (MDP) 触发后，将炎症性 Ly6C 单核细胞转化为巡逻 Ly6C 单核细胞。MDP 给药于缺乏 Ly6C 单核细胞的 Nr4a1 小鼠或 Ly6C 耗竭小鼠，导致具有类似于 Ly6C 单核细胞特征的血液巡逻单核细胞的出现，包括高表达 CX3CR1 和 LFA1。在炎症性疾病的动物模型中使用活体显微镜，我们还发现转化的 Ly6C 单核细胞在血管内皮细胞中巡逻，并且它们的存在有助于减少 MDP 注射后的炎症反应。我们的研究结果表明 NOD2 有助于调节血液单核细胞，并提示它可以作为治疗炎症性疾病的治疗靶点。
