Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Department of Genetics, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Nat Commun. 2020 May 21;11(1):2552. doi: 10.1038/s41467-020-16355-w.
Whereas microglia are recognized as fundamental players in central nervous system (CNS) development and function, much less is known about macrophages of the peripheral nervous system (PNS). Here, by comparing gene expression across neural and conventional tissue-resident macrophages, we identified transcripts that were shared among neural resident macrophages as well as selectively enriched in PNS macrophages. Remarkably, PNS macrophages constitutively expressed genes previously identified to be upregulated by activated microglia during aging, neurodegeneration, or loss of Sall1. Several microglial activation-associated and PNS macrophage-enriched genes were also expressed in spinal cord microglia at steady state. We further show that PNS macrophages rely on IL-34 for maintenance and arise from both embryonic and hematopoietic precursors, while their expression of activation-associated genes did not differ by ontogeny. Collectively, these data uncover shared and unique features between neural resident macrophages and emphasize the role of nerve environment for shaping PNS macrophage identity.
虽然小胶质细胞被认为是中枢神经系统 (CNS) 发育和功能的基本组成部分，但人们对周围神经系统 (PNS) 的巨噬细胞知之甚少。在这里，我们通过比较神经和传统组织驻留巨噬细胞中的基因表达，鉴定出了在神经驻留巨噬细胞中共享的转录本，以及在 PNS 巨噬细胞中选择性富集的转录本。值得注意的是，PNS 巨噬细胞组成性表达先前在衰老、神经退行性变或 Sall1 缺失过程中被激活的小胶质细胞上调的基因。一些与小胶质细胞激活相关的和 PNS 巨噬细胞中富集的基因在稳态时也在脊髓小胶质细胞中表达。我们进一步表明，PNS 巨噬细胞依赖 IL-34 维持其状态，并且来源于胚胎和造血前体，而其激活相关基因的表达与其发生方式无关。总的来说，这些数据揭示了神经驻留巨噬细胞之间的共同和独特特征，并强调了神经环境在塑造 PNS 巨噬细胞特征方面的作用。
