Reduced incidence and severity of antigen-induced autoimmune diseases in mice lacking interferon regulatory factor-1.
Interferon regulatory factor-1 (IRF-1) is a transcription factor that regulates interferon-induced genes and type I interferons. Recently, studies of IRF-l-deficient mice have revealed that IRF-I regulates the induction of molecules that play important roles in inflammation, such as inducible nitric oxide synthase (iNOS) and interleukin-l beta-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-l +/- mice, as was the production of interferon (IFN)-gamma in lymph node cells. Both IRF-l+/- 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-I plays a key role in promoting inflammation and autoimmunity in CIA and EAE animal models.
Tada
Y
Y
Amgen Institute, Department of Medical Biophysics, University of Toronto, Ontario, Canada.
Ho
A
A
Matsuyama
T
T
Mak
T W
TW
D000818:Animals; D000941:Antigens / Q000633:toxicity*; D001169:Arthritis, Experimental / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D004268:DNA-Binding Proteins / Q000235:genetics*; D004198:Disease Susceptibility / Q000276:immunology; D018836:Inflammation Mediators / Q000276:immunology; D050856:Interferon Regulatory Factor-1; D007371:Interferon-gamma / Q000096:biosynthesis; D007596:Joints / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D019001:Nitric Oxide Synthase / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012720:Severity of Illness Index; D013116:Spinal Cord / Q000201:enzymology / Q000378:metabolism
D000941:Antigens; D004268:DNA-Binding Proteins; D018836:Inflammation Mediators; D050856:Interferon Regulatory Factor-1; C494258:Irf1 protein, mouse; D010750:Phosphoproteins; D012333:RNA, Messenger; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase