IMMUNOBIOLOGY CD 141 1 dendritic cells produce prominent amounts of IFN - a after dsRNA recognition and can be targeted via DEC - 205 in humanized mice

Functional differences between human dendritic cell (DC) subsets and the potential benefits of targeting them with vaccines remain poorly defined. Here we describe that mice with reconstituted human immune system components (huNSG mice) develop all human conventional and plasmacytoid DC compartments in lymphoid organs. Testing different Toll-like receptor agonists for DC maturation in vivo, we found that IL-12p70 and interferon (IFN)-� production correlated with the maturation of CD141+ (BDCA3+) conventional DCs in huNSG mice. Furthermore, depletion of CD141+ DCs before stimulation significantly reduced IFN-� levels in vivo. This DC subset produced similar total amounts but different subtypes of IFN-� in response to synthetic double-stranded RNA compared with plasmacytoid DCs in response to a single-stranded RNA equivalent. Moreover, synthetic double-stranded RNA as adjuvant and antigen targeting to the endocytic receptor DEC-205, a combination that focuses antigen presentation for T-cell priming on CD141+ DCs, stimulated antigen-specific human CD4+ T-cell responses. Thus, the human CD141+ DC subset is a prominent source of IFN-� and interleukin-12 production and should be further evaluated for vaccine development. DOI: https://doi.org/10.1182/blood-2012-12-473413 Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-90078 Published Version Originally published at: Meixlsperger, Sonja; Leung, Carol S; Rämer, Patrick C; Pack, Maggi; Vanoaica, Liliana D; Breton, Gaëlle; Pascolo, Steve; Salazar, Andres M; Dzionek, Andrzej; Schmitz, Jürgen; Steinman, Ralph M; Münz, Christian (2013). CD141+ dendritic cells produce prominent amounts of IFN-� after dsRNA recognition and can be targeted via DEC-205 in humanized mice. Blood, 121(25):5034-5044. DOI: https://doi.org/10.1182/blood-2012-12-473413 doi:10.1182/blood-2012-12-473413 Prepublished online March 12, 2013; 2013 121: 5034-5044 and Christian Münz Breton, Steve Pascolo, Andres M. Salazar, Andrzej Dzionek, Jürgen Schmitz, Ralph M. Steinman Sonja Meixlsperger, Carol S. Leung, Patrick C. Rämer, Maggi Pack, Liliana D. Vanoaica, Gaëlle dsRNA recognition and can be targeted via DEC-205 in humanized mice after α CD141+ dendritic cells produce prominent amounts of IFNhttp://bloodjournal.hematologylibrary.org/content/121/25/5034.full.html Updated information and services can be found at: (5026 articles) Immunobiology • Articles on similar topics can be found in the following Blood collections http://bloodjournal.hematologylibrary.org/site/misc/rights.xhtml#repub_requests Information about reproducing this article in parts or in its entirety may be found online at: http://bloodjournal.hematologylibrary.org/site/misc/rights.xhtml#reprints Information about ordering reprints may be found online at: http://bloodjournal.hematologylibrary.org/site/subscriptions/index.xhtml Information about subscriptions and ASH membership may be found online at: Copyright 2011 by The American Society of Hematology; all rights reserved. Washington DC 20036. by the American Society of Hematology, 2021 L St, NW, Suite 900, Blood (print ISSN 0006-4971, online ISSN 1528-0020), is published weekly For personal use only. at Universitaet Zurich on June 21, 2013. bloodjournal.hematologylibrary.org From