%0 Journal Article
%A Fülle, Lorenz
%A Offermann, Nina
%A Hansen, Jan Niklas
%A Breithausen, Björn
%A Erazo, Anna Belen
%A Schanz, Oliver
%A Radau, Luca
%A Gondorf, Fabian
%A Knöpper, Konrad
%A Alferink, Judith
%A Abdullah, Zeinab
%A Neumann, Harald
%A Weighardt, Heike
%A Henneberger, Christian
%A Halle, Annett
%A Förster, Irmgard
%T CCL17 exerts a neuroimmune modulatory function and is expressed in hippocampal neurons.
%J Glia
%V 66
%N 10
%@ 0894-1491
%C Bognor Regis [u.a.]
%I Wiley-Liss
%M DZNE-2020-06662
%P 2246-2261
%D 2018
%X 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.
%K Animals
%K Chemokine CCL17: genetics
%K Chemokine CCL17: metabolism
%K Chemokine CCL22: metabolism
%K Female
%K Gene Expression
%K Granulocyte-Macrophage Colony-Stimulating Factor: metabolism
%K Green Fluorescent Proteins: genetics
%K Green Fluorescent Proteins: metabolism
%K Hippocampus: immunology
%K Hippocampus: pathology
%K Homeostasis: physiology
%K Inflammation: metabolism
%K Inflammation: pathology
%K Lipopolysaccharides
%K Male
%K Mice, Inbred C57BL
%K Mice, Transgenic
%K Microglia: immunology
%K Microglia: pathology
%K Monocytes: immunology
%K Monocytes: pathology
%K Neuroimmunomodulation: physiology
%K Neurons: immunology
%K Neurons: pathology
%K Receptors, CCR4: metabolism
%K Synaptic Transmission: physiology
%K Tumor Necrosis Factor-alpha: metabolism
%K Ccl17 protein, mouse (NLM Chemicals)
%K Ccl22 protein, mouse (NLM Chemicals)
%K Ccr4 protein, mouse (NLM Chemicals)
%K Chemokine CCL17 (NLM Chemicals)
%K Chemokine CCL22 (NLM Chemicals)
%K Lipopolysaccharides (NLM Chemicals)
%K Receptors, CCR4 (NLM Chemicals)
%K Tumor Necrosis Factor-alpha (NLM Chemicals)
%K enhanced green fluorescent protein (NLM Chemicals)
%K Green Fluorescent Proteins (NLM Chemicals)
%K Granulocyte-Macrophage Colony-Stimulating Factor (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:30277599
%R 10.1002/glia.23507
%U https://pub.dzne.de/record/140340