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Immunity. 2019 Jun 18;50(6):1453-1466.e4. doi: 10.1016/j.immuni.2019.04.002. Epub 2019 Apr 30.

Lymphatic Endothelial Cells Are Essential Components of the Subcapsular Sinus Macrophage Niche.

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Aix Marseille Univ, CNRS, INSERM, CIML, Marseille, France.
Institute of Systems Immunology, University of Würzburg, 97078 Würzburg, Germany.
Department of Biochemistry and Structural Biology, University of Texas Health Science Center, San Antonio, TX 78229, USA.
Aix Marseille Univ, CNRS, INSERM, CIML, Marseille, France. Electronic address:


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.


colony stimulating factor-1; homeostasis; lymph node; macrophages; niche; ontogeny; stromal cells

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