The Journal of Experimental Medicine
VeriKine-HS Human IFN-Beta
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 298K)
Right arrow PPT slides of all figures
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 Tada, Y.
Right arrow Articles by Mak, T. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tada, Y.
Right arrow Articles by Mak, T. W.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?
© The Rockefeller University Press, 0022-1007/1997/1/231/ $5.00
The Journal of Experimental Medicine, Volume 185, Number 2, January 20, 1997 231-238

Articles

Reduced Incidence and Severity of Antigen-induced Autoimmune Diseases in Mice Lacking Interferon Regulatory Factor-1

Yoshifumi Tada, Alexandra Ho, Toshifumi Matsuyama, and Tak W. Mak

From the Amgen Institute, Ontario Cancer Institute, and Departments of Medical Biophysics and Immunology, University of Toronto, Toronto, Ontario, Canada M5G 2C1

Interferon regulatory factor-1 (IRF-1) is a transcription factor that regulates interferon-induced genes and type I interferons. Recently, studies of IRF-1-deficient mice have revealed that IRF-1 regulates the induction of molecules that play important roles in inflammation, such as inducible nitric oxide synthase (iNOS) and interleukin-1β-converting enzyme (ICE). To study the role of IRF-1 in autoimmunity, we investigated type II collagen-induced arthritis (CIA), and experimental allergic encephalomyelitis (EAE), in mice lacking IRF-1. The incidence and severity of CIA were significantly decreased in IRF-1–/– mice compared with IRF-1+/– mice, as was the production of interferon (IFN)-{gamma} in lymph node cells. Both IRF-1+/– and IRF-1–/– mice exhibited mild and transient disease after adoptive transfer of a type II collagen (CII)-specific T cell line together with sera from arthritic mice, but the IRF-1–/– mice were less severely affected than the IRF-1+/– mice. In addition, the incidence of EAE in IRF-1–/– mice was decreased as compared with IRF-1+/– mice. Reverse transcription polymerase chain reaction showed that IRF-1 mRNA was constitutively expressed in the spinal cords of IRF-1+/– mice, and was upregulated in mice with clinical EAE. Expression of iNOS was also detected in inflamed spinal cords. These results suggest that IRF-1 plays a key role in promoting inflammation and autoimmunity in CIA and EAE animal models.

Address correspondence to Dr. Tak W. Mak, Amgen Institute, 620 University Avenue, Toronto, Ontario, Canada M5G 2C1.

This study is supported by Medical Research Council of Canada.

1Abbreviations used in this paper: CIA, collagen-induced arthritis; CII, type II collagen; EAE, experimental allergic encephalomyelitis; ICE, interleukin-1β-converting enzyme; iNOS, inducible nitric oxide synthase; IRF-1, interferon regulatory factor-1; ISRE, IFN-stimulated response element; NO, nitric oxide; NOD, nonobese diabetes.


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 Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:



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