CD141+ dendritic cells produce prominent amounts of IFN-α after dsRNA recognition and can be targeted via DEC-205 in humanized mice

Sonja Meixlsperger, Carol S. Leung, Patrick C. Rämer, Maggi Pack, Liliana D. Vanoaica, Gäelle Breton, Steve Pascolo, Andres M. Salazar, Andrzej Dzionek, Jürgen Schmitz, Ralph M. Steinman, Christian Münz

Research output: Contribution to journalArticlepeer-review

106 Scopus citations

Abstract

Functional differences between human dendritic cell (DC) subsets and the potential benefits of targeting themwith 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)-α production correlated with the maturation of CD141+ (BDCA3+) conventional DCs in huNSG mice. Furthermore, depletion of CD141+ DCs before stimulation significantly reduced IFN-α levels in vivo. This DC subset produced similar total amounts but different subtypes of IFN-α 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-α and interleukin-12 production and should be further evaluated for vaccine development.

Original languageEnglish
Pages (from-to)5034-5044
Number of pages11
JournalBlood
Volume121
Issue number25
DOIs
StatePublished - 20 Jun 2013
Externally publishedYes

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