淋巴内皮细胞是被膜下窦巨噬细胞生态位的必需组成部分。
Lymphatic Endothelial Cells Are Essential Components of the Subcapsular Sinus Macrophage Niche.
机构信息
Aix Marseille Univ, CNRS, INSERM, CIML, Marseille, France.
Institute of Systems Immunology, University of Würzburg, 97078 Würzburg, Germany.
出版信息
Immunity. 2019 Jun 18;50(6):1453-1466.e4. doi: 10.1016/j.immuni.2019.04.002. Epub 2019 Apr 30.
Abstract
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.
摘要
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。
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