The Journal of Experimental Medicine
PBL InterferonSource
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 18 July 2005. doi:10.1084/jem.20050338
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 202, Number 2, 321-331
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 3087K)
Right arrow PPT slides of all figures
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 Christensen, S. R.
Right arrow Articles by Shlomchik, M. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Christensen, S. R.
Right arrow Articles by Shlomchik, M. J.
Right arrowPubmed/NCBI databases
*Gene*GEO Profiles
*HomoloGene*UniGene
*Substance via MeSH
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

 Toll-like receptor 9 controls anti-DNA autoantibody production in murine lupus

Sean R. Christensen1, Michael Kashgarian2, Lena Alexopoulou4, Richard A. Flavell1, Shizuo Akira5,6, and Mark J. Shlomchik1,3

1 Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06510
2 Department of Pathology, Yale University School of Medicine, New Haven, CT 06510
3 Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06510
4 Centre d'Immunologie de Marseille-Luminy, INSERM-CNRS, University of Mediterranee, Campus de Luminy, 13288 Marseille Cedex 09, France
5 Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Suita City, Osaka 565-0871, Japan
6 Akira Innate Immunity Project, Exploratory Research for Advanced Technology, Japan Science and Technology Corporation, Osaka 565-0871, Japan

CORRESPONDENCE Mark J. Shlomchik: mark.shlomchik{at}yale.edu

Systemic autoimmune disease in humans and mice is characterized by loss of immunologic tolerance to a restricted set of self-nuclear antigens. Autoantigens, such as double-stranded (ds) DNA and the RNA-containing Smith antigen (Sm), may be selectively targeted in systemic lupus erythematosus because of their ability to activate a putative common receptor. Toll-like receptor 9 (TLR9), a receptor for CpG DNA, has been implicated in the activation of autoreactive B cells in vitro, but its role in promoting autoantibody production and disease in vivo has not been determined. We show that in TLR9-deficient lupus-prone mice, the generation of anti-dsDNA and antichromatin autoantibodies is specifically inhibited. Other autoantibodies, such as anti-Sm, are maintained and even increased in TLR9-deficient mice. In contrast, ablation of TLR3, a receptor for dsRNA, did not inhibit the formation of autoantibodies to either RNA- or DNA-containing antigens. Surprisingly, we found that despite the lack of anti-dsDNA autoantibodies in TLR9-deficient mice, there was no effect on the development of clinical autoimmune disease or nephritis. These results demonstrate a specific requirement for TLR9 in autoantibody formation in vivo and indicate a critical role for innate immune activation in autoimmunity.

Abbreviations used: ANA, antinuclear antibody; BCR, B cell receptor; ds, double-stranded; PAS, periodic acid Schiff; SLE, systemic lupus erythematosus; Sm, Smith antigen; snRNP, small nuclear ribonucleoprotein; ss, single-stranded; Toll-like receptor, TLR.


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