Aix-Marseille University, Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Immunologie de Marseille-Luminy (CIML), Marseille, France.
Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, IMMUNOS Building #3-4, BIOPOLIS, 138648, Singapore; Shanghai Institute of Immunology, Shanghai JiaoTong University School of Medicine, 280 South Chongqing Road, Shanghai 200025, China.
Cell Immunol. 2018 Aug;330:5-15. doi: 10.1016/j.cellimm.2018.01.001. Epub 2018 Jan 12.
Tissue-resident macrophages have pivotal functions for tissue defense and homeostasis. Two main discoveries have changed our current understanding of macrophage development: Their embryonic origin and their ability to self-renew throughout the lifespan. It is now well accepted that most tissue-resident macrophages are long-lived cells derived from a transient hematopoietic wave of erythro-myeloid progenitors (EMPs) emerging in the yolk sac. At least two distinct pathways derived from EMPs have been implicated in macrophage development. The first one, c-Myb-independent is giving rise to yolk sac macrophages also called primitive macrophages, and bypassing the classical monocytic intermediates. The second requires c-Myb expression and start once EMPs seed the fetal liver where they generate fetal monocytes. Sequentially, primitive macrophages seed every tissue and will ultimately give rise to microglia in the brain, rapidly isolated by the blood brain barrier, while EMP-derived fetal monocytes infiltrate every other tissues and gradually generate the major pool of adult tissue-resident macrophages by diluting the initial primitive macrophage contribution. A third wave of hematopoietic stem cells (HSC)-derived monocytes is also emerging from the fetal liver to contribute to the long-lived macrophage pool established at birth while the adult hematopoiesis is only starting in the bone marrow. We propose here to review recent insights about the different embryonic hematopoietic programs responsible for the generation of long-lived tissue-resident macrophages and their maintenance after birth.
组织驻留巨噬细胞在组织防御和稳态中具有关键功能。两个主要的发现改变了我们对巨噬细胞发育的现有认识：它们的胚胎起源和它们在整个生命周期中自我更新的能力。现在人们普遍认为，大多数组织驻留巨噬细胞是源自卵黄囊中出现的短暂造血红-髓祖细胞 (EMPs) 的长寿细胞。至少有两种不同的途径与巨噬细胞的发育有关。第一种途径是 c-Myb 非依赖性的，产生卵黄囊巨噬细胞，也称为原始巨噬细胞，并绕过经典的单核细胞中间阶段。第二种途径需要 c-Myb 的表达，一旦 EMP 定植于胎儿肝脏，就会产生胎儿单核细胞。随后，原始巨噬细胞定植于每个组织，并最终在大脑中产生小胶质细胞，这些细胞被血脑屏障迅速隔离，而 EMP 衍生的胎儿单核细胞浸润到其他组织中，并通过稀释最初的原始巨噬细胞的贡献，逐渐产生主要的成年组织驻留巨噬细胞池。第三波造血干细胞 (HSC) 衍生的单核细胞也从胎儿肝脏中出现，有助于在出生时建立的长寿巨噬细胞池的建立，而成年造血仅在骨髓中开始。在这里，我们建议回顾最近关于不同的胚胎造血程序的见解，这些程序负责产生长寿的组织驻留巨噬细胞及其在出生后的维持。
