TY  - JOUR
AU  - Fülle, Lorenz
AU  - Offermann, Nina
AU  - Hansen, Jan Niklas
AU  - Breithausen, Björn
AU  - Erazo, Anna Belen
AU  - Schanz, Oliver
AU  - Radau, Luca
AU  - Gondorf, Fabian
AU  - Knöpper, Konrad
AU  - Alferink, Judith
AU  - Abdullah, Zeinab
AU  - Neumann, Harald
AU  - Weighardt, Heike
AU  - Henneberger, Christian
AU  - Halle, Annett
AU  - Förster, Irmgard
TI  - CCL17 exerts a neuroimmune modulatory function and is expressed in hippocampal neurons.
JO  - Glia
VL  - 66
IS  - 10
SN  - 0894-1491
CY  - Bognor Regis [u.a.]
PB  - Wiley-Liss
M1  - DZNE-2020-06662
SP  - 2246-2261
PY  - 2018
AB  - 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.
KW  - Animals
KW  - Chemokine CCL17: genetics
KW  - Chemokine CCL17: metabolism
KW  - Chemokine CCL22: metabolism
KW  - Female
KW  - Gene Expression
KW  - Granulocyte-Macrophage Colony-Stimulating Factor: metabolism
KW  - Green Fluorescent Proteins: genetics
KW  - Green Fluorescent Proteins: metabolism
KW  - Hippocampus: immunology
KW  - Hippocampus: pathology
KW  - Homeostasis: physiology
KW  - Inflammation: metabolism
KW  - Inflammation: pathology
KW  - Lipopolysaccharides
KW  - Male
KW  - Mice, Inbred C57BL
KW  - Mice, Transgenic
KW  - Microglia: immunology
KW  - Microglia: pathology
KW  - Monocytes: immunology
KW  - Monocytes: pathology
KW  - Neuroimmunomodulation: physiology
KW  - Neurons: immunology
KW  - Neurons: pathology
KW  - Receptors, CCR4: metabolism
KW  - Synaptic Transmission: physiology
KW  - Tumor Necrosis Factor-alpha: metabolism
KW  - Ccl17 protein, mouse (NLM Chemicals)
KW  - Ccl22 protein, mouse (NLM Chemicals)
KW  - Ccr4 protein, mouse (NLM Chemicals)
KW  - Chemokine CCL17 (NLM Chemicals)
KW  - Chemokine CCL22 (NLM Chemicals)
KW  - Lipopolysaccharides (NLM Chemicals)
KW  - Receptors, CCR4 (NLM Chemicals)
KW  - Tumor Necrosis Factor-alpha (NLM Chemicals)
KW  - enhanced green fluorescent protein (NLM Chemicals)
KW  - Green Fluorescent Proteins (NLM Chemicals)
KW  - Granulocyte-Macrophage Colony-Stimulating Factor (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:30277599
DO  - DOI:10.1002/glia.23507
UR  - https://pub.dzne.de/record/140340
ER  -