Aix Marseille Univ, CNRS, INSERM, CIML, Marseille, France.
Institute of Systems Immunology, University of Würzburg, 97078 Würzburg, Germany.
Immunity. 2019 Jun 18;50(6):1453-1466.e4. doi: 10.1016/j.immuni.2019.04.002. Epub 2019 Apr 30.
In lymph nodes, subcapsular sinus macrophages (SSMs) form an immunological barrier that monitors lymph drained from peripheral tissues. Upon infection, SSMs activate B and natural killer T (NKT) cells while secreting inflammatory mediators. Here, we investigated the mechanisms regulating development and homeostasis of SSMs. Embryonic SSMs originated from yolk sac hematopoiesis and were replaced by a postnatal wave of bone marrow (BM)-derived monocytes that proliferated to establish the adult SSM network. The SSM network self-maintained by proliferation with minimal BM contribution. Upon pathogen-induced transient deletion, BM-derived cells contributed to restoring the SSM network. Lymphatic endothelial cells (LECs) were the main source of CSF-1 within the lymph node and conditional deletion of Csf1 in adult LECs decreased the network of SSMs and medullary sinus macrophages (MSMs). Thus, SSMs have a dual hematopoietic origin, and LECs are essential to the niche supporting these macrophages.
在淋巴结中，被膜下窦巨噬细胞（SSM）形成了一个免疫屏障，监测从外周组织引流的淋巴液。在感染时，SSM 会激活 B 细胞和自然杀伤 T 细胞（NKT），同时分泌炎症介质。在这里，我们研究了调节 SSM 发育和稳态的机制。胚胎 SSM 起源于卵黄囊造血，随后被骨髓（BM）来源的单核细胞替代，这些单核细胞增殖形成了成年 SSM 网络。SSM 网络通过增殖自我维持，很少需要 BM 的贡献。在病原体诱导的短暂缺失后，BM 来源的细胞有助于恢复 SSM 网络。淋巴管内皮细胞（LEC）是淋巴结内 CSF-1 的主要来源，在成年 LEC 中条件性缺失 Csf1 会减少 SSM 和髓窦巨噬细胞（MSM）网络。因此，SSM 具有双重造血起源，而 LEC 对支持这些巨噬细胞的龛位是必不可少的。
