Blood online
Home About Blood Authors Subscriptions Permission Advertising Public Access contact us
 

 
Advanced
Current Issue
First Edition
Archives
Submit to Blood
Search
American Society of Hematology
Meeting Abstracts
Email Alerts
Blood, 15 April 2008, Vol. 111, No. 8, pp. 4245-4253.
Prepublished online as a Blood First Edition Paper on February 7, 2008; DOI 10.1182/blood-2007-03-081398.


This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Figures
Right arrow All Versions of this Article:
blood-2007-03-081398v1
111/8/4245    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Right arrow Rights and Permissions
Citing Articles
Right arrow Citing Articles via CrossRef
Google Scholar
Right arrow Articles by Meyer-Wentrup, F.
Right arrow Articles by Adema, G. J.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Meyer-Wentrup, F.
Right arrow Articles by Adema, G. J.
Related Collections
Right arrow Chemokines, Cytokines, and Interleukins
Right arrow Immunobiology
Social Bookmarking
 Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

arrow to previous article Previous Article  |  Table of Contents  |  Next Article next article arrow

IMMUNOBIOLOGY

Targeting DCIR on human plasmacytoid dendritic cells results in antigen presentation and inhibits IFN-{alpha} production

Friederike Meyer-Wentrup1, Daniel Benitez-Ribas1, Paul J. Tacken1, Cornelis J. A. Punt2, Carl G. Figdor1, I. Jolanda M. de Vries1, and Gosse J. Adema1

Departments of1 Tumor Immunology and 2 Medical Oncology, Radboud University Nijmegen Medical Centre and Nijmegen Centre for Molecular Life Sciences, Nijmegen, The Netherlands

C-type lectin receptors (CLRs) fulfill multiple functions within the immune system by recognition of carbohydrate moieties on foreign or (altered) self-structures. CLRs on myeloid dendritic cells (DCs) have been well characterized as pattern-recognition receptors (PRRs) combining ligand internalization with complex signaling events. Much less is known about CLR expression and function in human plasmacytoid DCs (pDCs), the major type I interferon (IFN) producers. In this study, we demonstrate that, next to the CLR BDCA-2, human pDCs express DC immunoreceptor (DCIR), a CLR with putative immune-inhibitory function, but not dectin-1, mannose receptor, or DC-specific ICAM-3–grabbing nonintegrin. DCIR surface levels are reduced on pDC maturation after TLR9 triggering. Interestingly, DCIR triggering inhibits TLR9-induced IFN-{alpha} production while leaving up-regulation of costimulatory molecule expression unaffected. Furthermore, DCIR is readily internalized into pDCs after receptor triggering. We show that DCIR internalization is clathrin-dependent because it can be inhibited by hypertonic shock and dominant-negative dynamin. Importantly, antigens targeted to pDCs via DCIR are presented to T cells. These findings indicate that targeting DCIR on pDCs not only results in efficient antigen presentation but also affects TLR9-induced IFN-{alpha} production. Collectively, the data show that targeting of DCIR can modulate human pDC function and may be applied in disease preven-tion and treatment.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?




 click for free articles
home about blood authors subscriptions permissions advertising public access contact us
Sponsor: Genentech BioOncology and and Biogen Idec
Blood Online is supported in part by
Genentech BioOncology and Biogen Idec
  Copyright © 2008 by American Society of Hematology         Online ISSN: 1528-0020