The Journal of Experimental Medicine
Ancell Corp.
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online September 24, 2007
doi:10.1084/jem.20070814
The Journal of Experimental Medicine, Vol. 204, No. 10, 2423-2437
The Rockefeller University Press, 0022-1007 $30.00
© 2007 Decalf et al.
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Material Index
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Decalf, J.
Right arrow Articles by Albert, M. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Decalf, J.
Right arrow Articles by Albert, M. L.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

ARTICLE

 Plasmacytoid dendritic cells initiate a complex chemokine and cytokine network and are a viable drug target in chronic HCV patients

Jérémie Decalf1, Sandrine Fernandes2, Randy Longman1,4, Mina Ahloulay2, Françoise Audat3, François Lefrerre3, Charles M. Rice4, Stanislas Pol2, and Matthew L. Albert1,5

1 The Laboratory of Dendritic Cell Biology, Department of Immunology, Institut Pasteur, 75724 Paris, Cedex 15, France
2 Institut National de la Santé et de la Recherche Médicale, U370, The Liver Unit, 75013 Paris, France
3 The Division of Transfusion Medicine, Necker Hospital, 75015 Paris, Cedex 15, France
4 The Rockefeller University, New York, NY 10065
5 Institut National de la Santé et de la Recherche Médicale, U818, Paris, France

CORRESPONDENCE Matthew L. Albert: albertm{at}pasteur.fr

Plasmacytoid dendritic cells (pDCs) are the professional type I interferon (IFN)-producing cells, and upon activation they traffic to lymph organs, where they bridge innate and adaptive immunity. Using multianalyte profiling (MAP), we have mapped the key chemokines and cytokines produced in response to pDC activation, taking into consideration the role of autocrine IFN, as well as paracrine effects on other innate cells (e.g., monocytes and conventional DCs). Interestingly, we identify four distinct cytokine/chemokine loops initiated by Toll-like receptor engagement. Finally, we applied this analytic approach to the study of pDC activity in chronic hepatitis C patients. Based on the activation state of pDCs in fresh blood, the lack of agonistic activity of infectious virions, the production of a broad array of cytokines/chemokines once stimulated, and the direct effects of pDCs on other PBMCs, we conclude that the pDCs from hepatitis C virus (HCV)-infected individuals are fully functional and are, indeed, a viable drug target. In sum, this study provides insight into the use of MAP technology for characterizing cytokine networks, and highlights how a rare cell type integrates the activation of other inflammatory cells. Furthermore, this work will help evaluate the therapeutic application of pDC agonists in diseases such as chronic HCV infection.

Abbreviations used: cDC, conventional DC; HAU, hemagglutinating unit; HCV, hepatitis C virus; HEV, high endothelial venule; IFNAR, interferon {alpha}/ß receptor; ICCS, intracellular cytokine stimulation; MAP, multianalyte profiling; NR, nonresponder; pDC, plasmacytoid DC; Rluc, Renilla luciferase; SVR, sustained virologic responder; TLR, Toll-like receptor.

S. Fernandes, R. Longman, and M. Ahloulay contributed equally to this paper.


Add to CiteULike CiteULike   Add to Complore Complore   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?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS