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@ARTICLE{Flle:140340,
author = {Fülle, Lorenz and Offermann, Nina and Hansen, Jan Niklas
and Breithausen, Björn and Erazo, Anna Belen and Schanz,
Oliver and Radau, Luca and Gondorf, Fabian and Knöpper,
Konrad and Alferink, Judith and Abdullah, Zeinab and
Neumann, Harald and Weighardt, Heike and Henneberger,
Christian and Halle, Annett and Förster, Irmgard},
title = {{CCL}17 exerts a neuroimmune modulatory function and is
expressed in hippocampal neurons.},
journal = {Glia},
volume = {66},
number = {10},
issn = {0894-1491},
address = {Bognor Regis [u.a.]},
publisher = {Wiley-Liss},
reportid = {DZNE-2020-06662},
pages = {2246-2261},
year = {2018},
abstract = {Chemokines are important signaling molecules in the immune
and nervous system. Using a fluorescence reporter mouse
model, we demonstrate that the chemokine CCL17, a ligand of
the chemokine receptor CCR4, is produced in the murine
brain, particularly in a subset of hippocampal CA1 neurons.
We found that basal expression of Ccl17 in hippocampal
neurons was strongly enhanced by peripheral challenge with
lipopolysaccharide (LPS). LPS-mediated induction of Ccl17 in
the hippocampus was dependent on local tumor necrosis factor
(TNF) signaling, whereas upregulation of Ccl22 required
granulocyte-macrophage colony-stimulating factor (GM-CSF).
CCL17 deficiency resulted in a diminished microglia density
under homeostatic and inflammatory conditions. Further,
microglia from naïve Ccl17-deficient mice possessed a
reduced cellular volume and a more polarized process tree as
assessed by computer-assisted imaging analysis. Regarding
the overall branching, cell surface area, and total tree
length, the morphology of microglia from naïve
Ccl17-deficient mice resembled that of microglia from
wild-type mice after LPS stimulation. In line,
electrophysiological recordings indicated that CCL17
downmodulates basal synaptic transmission at CA3-CA1
Schaffer collaterals in acute slices from naïve but not
LPS-treated animals. Taken together, our data identify CCL17
as a homeostatic and inducible neuromodulatory chemokine
affecting the presence and morphology of microglia and
synaptic transmission in the hippocampus.},
keywords = {Animals / Chemokine CCL17: genetics / Chemokine CCL17:
metabolism / Chemokine CCL22: metabolism / Female / Gene
Expression / Granulocyte-Macrophage Colony-Stimulating
Factor: metabolism / Green Fluorescent Proteins: genetics /
Green Fluorescent Proteins: metabolism / Hippocampus:
immunology / Hippocampus: pathology / Homeostasis:
physiology / Inflammation: metabolism / Inflammation:
pathology / Lipopolysaccharides / Male / Mice, Inbred C57BL
/ Mice, Transgenic / Microglia: immunology / Microglia:
pathology / Monocytes: immunology / Monocytes: pathology /
Neuroimmunomodulation: physiology / Neurons: immunology /
Neurons: pathology / Receptors, CCR4: metabolism / Synaptic
Transmission: physiology / Tumor Necrosis Factor-alpha:
metabolism / Ccl17 protein, mouse (NLM Chemicals) / Ccl22
protein, mouse (NLM Chemicals) / Ccr4 protein, mouse (NLM
Chemicals) / Chemokine CCL17 (NLM Chemicals) / Chemokine
CCL22 (NLM Chemicals) / Lipopolysaccharides (NLM Chemicals)
/ Receptors, CCR4 (NLM Chemicals) / Tumor Necrosis
Factor-alpha (NLM Chemicals) / enhanced green fluorescent
protein (NLM Chemicals) / Green Fluorescent Proteins (NLM
Chemicals) / Granulocyte-Macrophage Colony-Stimulating
Factor (NLM Chemicals)},
cin = {U Preclinical Researchers - Bonn / AG Halle},
ddc = {610},
cid = {I:(DE-2719)7000005 / I:(DE-2719)1013034},
pnm = {342 - Disease Mechanisms and Model Systems (POF3-342)},
pid = {G:(DE-HGF)POF3-342},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:30277599},
doi = {10.1002/glia.23507},
url = {https://pub.dzne.de/record/140340},
}