Journal Article

DZNE-2020-06662

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png CCL17 exerts a neuroimmune modulatory function and is expressed in hippocampal neurons.

Fülle, L. ; Offermann, N. ; Hansen, J. N. ; Breithausen, B. ; Erazo, A. B. ; Schanz, O. ; Radau, L. ; Gondorf, F. ; Knöpper, K. ; Alferink, J. ; Abdullah, Z. ; Neumann, H. ; Weighardt, H. ; Henneberger, C.DZNE* ; Halle, A.DZNE* ; Förster, I. (Corresponding author)

2018
Wiley-Liss Bognor Regis [u.a.]

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Please use a persistent id in citations: doi:10.1002/glia.23507

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.

Keyword(s): Animals (MeSH) ; Chemokine CCL17: genetics (MeSH) ; Chemokine CCL17: metabolism (MeSH) ; Chemokine CCL22: metabolism (MeSH) ; Female (MeSH) ; Gene Expression (MeSH) ; Granulocyte-Macrophage Colony-Stimulating Factor: metabolism (MeSH) ; Green Fluorescent Proteins: genetics (MeSH) ; Green Fluorescent Proteins: metabolism (MeSH) ; Hippocampus: immunology (MeSH) ; Hippocampus: pathology (MeSH) ; Homeostasis: physiology (MeSH) ; Inflammation: metabolism (MeSH) ; Inflammation: pathology (MeSH) ; Lipopolysaccharides (MeSH) ; Male (MeSH) ; Mice, Inbred C57BL (MeSH) ; Mice, Transgenic (MeSH) ; Microglia: immunology (MeSH) ; Microglia: pathology (MeSH) ; Monocytes: immunology (MeSH) ; Monocytes: pathology (MeSH) ; Neuroimmunomodulation: physiology (MeSH) ; Neurons: immunology (MeSH) ; Neurons: pathology (MeSH) ; Receptors, CCR4: metabolism (MeSH) ; Synaptic Transmission: physiology (MeSH) ; Tumor Necrosis Factor-alpha: metabolism (MeSH) ; Ccl17 protein, mouse ; Ccl22 protein, mouse ; Ccr4 protein, mouse ; Chemokine CCL17 ; Chemokine CCL22 ; Lipopolysaccharides ; Receptors, CCR4 ; Tumor Necrosis Factor-alpha ; enhanced green fluorescent protein ; Green Fluorescent Proteins ; Granulocyte-Macrophage Colony-Stimulating Factor

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Contributing Institute(s):

1. U Preclinical Researchers - Bonn (U Preclinical Researchers - Bonn)
2. Microglia and Neuroinflammation (AG Halle)

Research Program(s):

1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)

Appears in the scientific report 2018

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; IF >= 5 ; JCR ; Nationallizenz ; SCOPUS ; Web of Science Core Collection

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