成年大脑中的小胶质细胞仅在特定宿主条件下源自Ly-6ChiCCR2+单核细胞。

Microglia in the adult brain arise from Ly-6ChiCCR2+ monocytes only under defined host conditions.

作者信息

Mildner Alexander, Schmidt Hauke, Nitsche Mirko, Merkler Doron, Hanisch Uwe-Karsten, Mack Matthias, Heikenwalder Mathias, Brück Wolfgang, Priller Josef, Prinz Marco

机构信息

Institute of Neuropathology, Georg August University, Göttingen, Germany.

出版信息

Nat Neurosci. 2007 Dec;10(12):1544-53. doi: 10.1038/nn2015. Epub 2007 Nov 18.

DOI:10.1038/nn2015

PMID:18026096

Abstract

Microglia are crucially important myeloid cells in the CNS and constitute the first immunological barrier against pathogens and environmental insults. The factors controlling microglia recruitment from the blood remain elusive and the direct circulating microglia precursor has not yet been identified in vivo. Using a panel of bone marrow chimeric and adoptive transfer experiments, we found that circulating Ly-6C(hi)CCR2(+) monocytes were preferentially recruited to the lesioned brain and differentiated into microglia. Notably, microglia engraftment in CNS pathologies, which are not associated with overt blood-brain barrier disruption, required previous conditioning of brain (for example, by direct tissue irradiation). Our results identify Ly-6C(hi)CCR2(+) monocytes as direct precursors of microglia in the adult brain and establish the importance of local factors in the adult CNS for microglia engraftment.

摘要

小胶质细胞是中枢神经系统中至关重要的髓样细胞，构成了抵御病原体和环境损伤的第一道免疫屏障。控制小胶质细胞从血液中募集的因素仍不清楚，并且尚未在体内鉴定出直接的循环小胶质细胞前体。通过一系列骨髓嵌合体和过继转移实验，我们发现循环中的Ly-6C(hi)CCR2(+)单核细胞优先被募集到受损脑区并分化为小胶质细胞。值得注意的是，在不伴有明显血脑屏障破坏的中枢神经系统病变中，小胶质细胞的植入需要预先对脑进行预处理（例如，通过直接组织照射）。我们的结果将Ly-6C(hi)CCR2(+)单核细胞鉴定为成人大脑中直接的小胶质细胞前体，并确立了成体中枢神经系统中局部因素对小胶质细胞植入的重要性。