Reduced incidence and severity of antigen-induced autoimmune diseases in mice lacking interferon regulatory factor-1

Abstract

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)-γ 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.