Institute of Brain Research, University of Tuebingen, Tuebingen, Germany.
Brain Res Bull. 2011 Oct 10;86(3-4):229-34. doi: 10.1016/j.brainresbull.2011.07.005. Epub 2011 Jul 18.
Experimental autoimmune neuritis (EAN) is a well-known animal model of human demyelinating polyneuropathies and is characterized by inflammation and demyelination in the peripheral nervous system. Tim-3 had been identified as a Th1-specific marker negatively regulating autoimmunity or inflammatory diseases. Here we have studied by immunohistochemistry the spatiotemporal accumulation of Tim-3(+) cells in sciatic nerves of EAN rats, particularly focusing on its association with alternatively activated macrophages. Our results showed that time course of Tim-3(+) cell accumulation correlated positively with disease progression of EAN; but distinct major cellular resources of Tim-3 were observed at different disease stages of EAN: during the early phase of EAN, the main cellular resource were T cells, but at the peak and during recovery phase of EAN, Tim-3 was mostly expressed on CD68(+) macrophages or CD163(+) cells. Further investigation suggested that accumulation of CD163(+) cells, particularly their relative abundances to activated macrophages at different time points, were in accordance with the recovery from EAN. Therefore, Tim3(+) cells might include a distinct macrophage population, which may be involved in anti-inflammatory effect and recovery from EAN.
实验性自身免疫性神经炎(EAN)是一种众所周知的人类脱髓鞘多发性神经病动物模型,其特征是在外周神经系统中发生炎症和脱髓鞘。Tim-3 已被确定为负调节自身免疫或炎症性疾病的 Th1 特异性标志物。在这里,我们通过免疫组织化学研究了 Tim-3(+)细胞在 EAN 大鼠坐骨神经中的时空积累,特别是重点关注其与交替激活的巨噬细胞的关联。我们的结果表明,Tim-3(+)细胞积累的时间进程与 EAN 的疾病进展呈正相关;但在 EAN 的不同疾病阶段观察到 Tim-3 的主要细胞来源不同:在 EAN 的早期阶段,主要的细胞来源是 T 细胞,但在 EAN 的高峰期和恢复期,Tim-3 主要表达在 CD68(+)巨噬细胞或 CD163(+)细胞上。进一步的研究表明,CD163(+)细胞的积累,特别是它们在不同时间点相对于活化巨噬细胞的相对丰度,与 EAN 的恢复一致。因此,Tim3(+)细胞可能包括一个独特的巨噬细胞群体,该群体可能参与 EAN 的抗炎作用和恢复。