Abstract / Description of output
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.
Original language | English |
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Pages (from-to) | 1453-1466.e4 |
Number of pages | 18 |
Journal | Immunity |
Volume | 50 |
Issue number | 6 |
Early online date | 30 Apr 2019 |
DOIs | |
Publication status | Published - 18 Jun 2019 |
Keywords / Materials (for Non-textual outputs)
- Animals
- Biomarkers
- Cell Communication
- Cell Differentiation
- Endothelial Cells/metabolism
- Gene Expression
- Genes, Reporter
- Hematopoiesis/genetics
- Homeostasis
- Lymph Nodes/cytology
- Lymphatic Vessels
- Macrophage Colony-Stimulating Factor/metabolism
- Macrophages/cytology
- Mice
- Monocytes/cytology
- Yolk Sac
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Rebecca Gentek
- Deanery of Clinical Sciences - Chancellors Research Fellow (PI)
- Centre for Inflammation Research
Person: Academic: Research Active