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Glia. 2018 Oct;66(10):2246-2261. doi: 10.1002/glia.23507. Epub 2018 Sep 12.

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

Author information

1
Immunology & Environment, Life and Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
2
Neuroimmunology, Center of Advanced European Studies and Research (CAESAR), Bonn, Germany.
3
Institute of Cellular Neurosciences, University of Bonn Medical School, Bonn, Germany.
4
Department of Psychiatry, University of Münster, Münster, Germany.
5
Institute of Experimental Immunology and Molecular Medicine, University of Bonn, Bonn, Germany.
6
Neural Regeneration Group, Institute of Reconstructive Neurobiology, University of Bonn, Bonn, Germany.
7
Institute of Neurology, University College London, London, United Kingdom.
8
German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.

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:

CCL17; CCL22; LPS-induced inflammation; hippocampus; microglia morphology; neuromodulatory chemokines; neuron-glia cross-talk

PMID:
30277599
DOI:
10.1002/glia.23507

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