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CCL17 exerts a neuroimmune modulatory function and is expressed in hippocampal neurons

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Titel: CCL17 exerts a neuroimmune modulatory function and is expressed in hippocampal neurons
Autoren: Harald Neumann, Nina Offermann, Anna Belen Erazo, Irmgard Förster, Luca Radau, Annett Halle, Zeinab Abdullah, Konrad Knöpper, Judith Alferink, Lorenz Fülle, Björn Breithausen, Fabian Gondorf, Heike Weighardt, Christian Henneberger, Oliver Schanz, Jan N. Hansen
Quelle: Glia 66(10), 2246-2261 (2018). doi:10.1002/glia.23507
Glia
Verlagsinformationen: Wiley, 2018.
Publikationsjahr: 2018
Schlagwörter: Lipopolysaccharides, Male, 0301 basic medicine, genetics [Chemokine CCL17], metabolism [Tumor Necrosis Factor-alpha], Gene Expression, enhanced green fluorescent protein, Hippocampus, Synaptic Transmission, Monocytes, pathology [Neurons], Homeostasis, 10. No inequality, immunology [Hippocampus], Neurons, metabolism [Inflammation], 0303 health sciences, pathology [Microglia], immunology [Microglia], metabolism [Chemokine CCL22], Female, Microglia, physiology [Homeostasis], Ccl22 protein, mouse, Ccl17 protein, mouse, metabolism [Receptors, CCR4], Receptors, CCR4, physiology [Neuroimmunomodulation], Neuroimmunomodulation, Green Fluorescent Proteins, Ccr4 protein, mouse, Mice, Transgenic, immunology [Monocytes], 03 medical and health sciences, metabolism [Chemokine CCL17], genetics [Green Fluorescent Proteins], Animals, ddc:610, pathology [Inflammation], Chemokine CCL22, Inflammation, metabolism [Granulocyte-Macrophage Colony-Stimulating Factor], pathology [Monocytes], Tumor Necrosis Factor-alpha, Granulocyte-Macrophage Colony-Stimulating Factor, Mice, Inbred C57BL, pathology [Hippocampus], physiology [Synaptic Transmission], metabolism [Green Fluorescent Proteins], Chemokine CCL17, immunology [Neurons]
Beschreibung: 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.
Publikationsart: Article
Dateibeschreibung: application/pdf
Sprache: English
ISSN: 1098-1136
0894-1491
DOI: 10.1002/glia.23507
Zugangs-URL: https://pubmed.ncbi.nlm.nih.gov/30277599
https://pubmed.ncbi.nlm.nih.gov/30277599/
https://www.ncbi.nlm.nih.gov/pubmed/30277599
https://onlinelibrary.wiley.com/doi/full/10.1002/glia.23507
https://pure.mpg.de/pubman/faces/ViewItemOverviewPage.jsp?itemId=item_3039249
https://pub.dzne.de/record/140340
http://hdl.handle.net/21.11116/0000-0003-4AD5-A
http://hdl.handle.net/21.11116/0000-0003-4AD7-8
Rights: Wiley Online Library User Agreement
Dokumentencode: edsair.doi.dedup.....df86cc571e4121cf189ad16e4394051c
Datenbank: OpenAIRE
Beschreibung
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.
ISSN:10981136
08941491
DOI:10.1002/glia.23507