Intestinal epithelial cell transported TLR2 ligand stimulates Ly6C+ monocyte differentiation in a G-CSF dependent manner

Microflora-induced TLR signaling in the intestinal epithelium is essential for a proper intestinal barrier function. Because of the close interactions of this epithelial layer with underlying mononuclear phagocytes, we hypothesized that epithelial TLR signaling may affect the differentiation of myel...

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Bibliographic Details
Published in:Immunobiology (1979) Vol. 220; no. 11; pp. 1255 - 1265
Main Authors: Hiemstra, Ida H., Vrijland, Kim, Hogenboom, Marye M., Bouma, Gerd, Kraal, Georg, den Haan, Joke M.M.
Format: Journal Article
Language:English
Published: Netherlands Elsevier GmbH 01.11.2015
Subjects:
Advanced Basic Science
Allergy and Immunology
Animals
Antigens, Ly - metabolism
Cell Differentiation - drug effects
Cells, Cultured
Dendritic cell
Dendritic Cells - cytology
Dendritic Cells - immunology
Dendritic Cells - metabolism
Granulocyte Colony-Stimulating Factor - biosynthesis
Granulocyte Colony-Stimulating Factor - pharmacology
Intestinal epithelial cells
Intestinal Mucosa - immunology
Intestinal Mucosa - metabolism
Intestinal Mucosa - microbiology
Leukocyte Count
Ligands
Lipopeptides - pharmacology
Mice
Microflora
Monocyte differentiation
Monocytes - drug effects
Monocytes - physiology
Toll-Like Receptor 2 - agonists
Toll-Like Receptor 2 - metabolism
Transcytosis
Dendritic cell
M-CSF
GM-CSF
Intestinal epithelial cells
Microflora
Flt3L
BM
TLR
G-CSF
Monocyte differentiation
DC
granulocyte macrophage colony-stimulating factor
FMS-like tyrosine kinase 3 ligand
granulocyte colony-stimulating factor
bone marrow
toll-like receptor
dendritic cell
macrophage colony-stimulating factor
ISSN:0171-2985, 1878-3279
Online Access:Get full text
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Summary:Microflora-induced TLR signaling in the intestinal epithelium is essential for a proper intestinal barrier function. Because of the close interactions of this epithelial layer with underlying mononuclear phagocytes, we hypothesized that epithelial TLR signaling may affect the differentiation of myeloid cell populations. In in vitro cultures we observed that colonic epithelial monolayers actively transported TLR2 ligands towards their basolateral side. The transported TLR2 ligands strongly stimulated the development of Ly6C+ monocytes, while dendritic cell differentiation was inhibited. The TLR2 effect on monocyte and dendritic cell differentiation was mediated by the production of G-CSF. Mice lacking TLR signaling and mice that were treated with antibiotics showed decreased numbers of Ly6C+ monocytes in bone marrow and spleen, which points to a role for microbial derived TLR-ligands in the homeostasis of Ly6C+ monocytes. In conclusion, our results indicate that TLR ligands that are transported by intestinal epithelial cells stimulate Ly6C+ monocyte development and suggest that this process may be involved in the maintenance of systemic Ly6C+ monocyte numbers.
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ISSN:0171-2985
1878-3279
DOI:10.1016/j.imbio.2015.06.015