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Tissue Distribution Dynamics of Human NK Cells Inferred from Peripheral Blood Depletion Kinetics after Sphingosine-1-Phosphate Receptor Blockade

Mehling, M. and Burgener, A. V. and Brinkmann, V. and Bantug, G. R. and Dimeloe, S. and Hoenger, G. and Kappos, L. and Hess, C.. (2015) Tissue Distribution Dynamics of Human NK Cells Inferred from Peripheral Blood Depletion Kinetics after Sphingosine-1-Phosphate Receptor Blockade. Scandinavian Journal of Immunology, 82 (5). pp. 460-466.

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Official URL: https://edoc.unibas.ch/61869/

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Abstract

Human natural killer (NK) cell subsets differentially distribute throughout the organism. While CD56(dim) and CD56(bright) NK cell subsets similarly reside in the bone marrow (BM), the CD56(dim) population predominantly accumulates in non-lymphoid tissues and the CD56(bright) counterpart in lymphoid tissue (LT). The dynamics with which these NK cell subsets redistribute to tissues remains unexplored. Here, we studied individuals newly exposed to fingolimod, a drug that efficiently blocks sphingosine-1-phosphate (S1P)-directed lymphocyte - including NK cell - egress from tissue to blood. During an observation period of 6h peripheral blood depletion of CD56(bright) NK cells was observed 3 h after first dose of fingolimod, with 40-50% depletion after 6 h, while a decrease of the numbers of CD56(dim) NK cells did not reach the level of statistical significance. In vitro, CD56(bright) and CD56(dim) NK cells responded comparably to the BM-homing chemokine CXCL12, while CD56(bright) NK cells migrated more efficiently in gradients of the LT-homing chemokines CCL19 and CCL21. In conjuncture with these in vitro studies, the indirectly observed subset-specific depletion kinetics from blood are compatible with preferential and more rapid redistribution of CD56(bright) NK cells from blood to peripheral tissue such as LT and possibly also the inflamed central nervous system. These data shed light on an unexplored level at which access of NK cells to LT, and thus, for example antigen-presenting cells, is regulated.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Immunobiology (Hess C)
03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Translational Neuroimmunology (Mehling)
UniBasel Contributors:Hess, Christoph and Mehling, Matthias
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Wiley-Blackwell - STM
ISSN:0300-9475
e-ISSN:1365-3083
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:06 Nov 2018 17:50
Deposited On:22 Oct 2018 16:44

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