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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-16721

Lünemann, A; Lünemann, J D; Roberts, S; Messmer, B; Barreira da Silva, R; Raine, C S; Münz, C (2008). Human NK cells kill resting but not activated microglia via NKG2D- and NKp46-mediated recognition. Journal of Immunology, 181(9):6170-6177.

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Abstract

Microglia are resident macrophage-like APCs of the CNS. To avoid escalation of inflammatory processes and bystander damage within the CNS, microglia-driven inflammatory responses need to be tightly regulated and both spatially and temporally restricted. Following traumatic, infectious, and autoimmune-mediated brain injury, NK cells have been found in the CNS, but the functional significance of NK cell recruitment and their mechanisms of action during brain inflammation are not well understood. In this study, we investigated whether and by which mechanisms human NK cells might edit resting and activated human microglial cells via killing in vitro. IL-2-activated NK cells efficiently killed both resting allogeneic and autologous microglia in a cell-contact-dependent manner. Activated NK cells rapidly formed synapses with human microglial cells in which perforin had been polarized to the cellular interface. Ab-mediated NKG2D and NKp46 blockade completely prevented the killing of human microglia by activated NK cells. Up-regulation of MHC class I surface expression by TLR4 stimulation protected microglia from NK cell-mediated killing, whereas MHC class I blockade enhanced cytotoxic NK cell activity. These data suggest that brain-infiltrating NK cells might restrict innate and adaptive immune responses within the human CNS via elimination of resting microglia.

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23 citations in Web of Science®
25 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Experimental Immunology
DDC:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2008
Deposited On:10 Jan 2010 13:20
Last Modified:20 Apr 2014 07:08
Publisher:American Association of Immunologists
ISSN:0022-1767
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:10.4049/jimmunol.181.9.6170
Related URLs:http://www.jimmunol.org/cgi/content/full/181/9/6170 (Publisher)
PubMed ID:18941207

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