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

Tada Y, Ho A, Matsuyama T, Mak TW - J. Exp. Med. (1997)

Bottom Line: Interferon regulatory factor-1 (IRF-1) is a transcription factor that regulates interferon-induced genes and type I interferons.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.Expression of iNOS was also detected in inflamed spinal cords.

View Article: PubMed Central - PubMed

Affiliation: Amgen Institute, Department of Medical Biophysics, University of Toronto, Ontario, Canada.

ABSTRACT
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.

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IFN-γ production of LN cells from CII-immunized IRF1+/− and IRF-1−/− DBA/1 mice. LN cells were prepared on day 14 or  day 21 after immunization and stimulated with dCII or anti-CD3. IFN-γ  production on day 14 was decreased by fourfold in IRF-1−/− mice (P  <0.05). Mean IFN-γ concentration ± SD from four (day 14) and two  (day 21) experiments is shown.
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Figure 3: IFN-γ production of LN cells from CII-immunized IRF1+/− and IRF-1−/− DBA/1 mice. LN cells were prepared on day 14 or day 21 after immunization and stimulated with dCII or anti-CD3. IFN-γ production on day 14 was decreased by fourfold in IRF-1−/− mice (P <0.05). Mean IFN-γ concentration ± SD from four (day 14) and two (day 21) experiments is shown.

Mentions: To analyze the antigen-specific T cell response in IRF-1+/− and IRF-1−/− DBA/1 mice, IFN-γ production by LN cells in response to dCII was examined. Mice were killed at 14 or 21 d after immunization, and LN cells were purified and stimulated with dCII or anti-CD3 antibodies. Anti-CD3 stimulation induced large amounts of IFN-γ secretion from LN cells in both groups of mice. However, as shown in Fig. 3, LN cells from IRF-1−/− mice secreted a reduced amount of IFN-γ in response to dCII as compared with IRF-1+/− mice on day 14. On day 21, IFN-γ production in response to dCII was decreased in IRF-1+/− mice, while it remained at low levels in IRF-1−/− mice. These results suggest that IFN-γ production by LN cells in response to dCII is defective in IRF-1−/− mice.


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

Tada Y, Ho A, Matsuyama T, Mak TW - J. Exp. Med. (1997)

IFN-γ production of LN cells from CII-immunized IRF1+/− and IRF-1−/− DBA/1 mice. LN cells were prepared on day 14 or  day 21 after immunization and stimulated with dCII or anti-CD3. IFN-γ  production on day 14 was decreased by fourfold in IRF-1−/− mice (P  <0.05). Mean IFN-γ concentration ± SD from four (day 14) and two  (day 21) experiments is shown.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196116&req=5

Figure 3: IFN-γ production of LN cells from CII-immunized IRF1+/− and IRF-1−/− DBA/1 mice. LN cells were prepared on day 14 or day 21 after immunization and stimulated with dCII or anti-CD3. IFN-γ production on day 14 was decreased by fourfold in IRF-1−/− mice (P <0.05). Mean IFN-γ concentration ± SD from four (day 14) and two (day 21) experiments is shown.
Mentions: To analyze the antigen-specific T cell response in IRF-1+/− and IRF-1−/− DBA/1 mice, IFN-γ production by LN cells in response to dCII was examined. Mice were killed at 14 or 21 d after immunization, and LN cells were purified and stimulated with dCII or anti-CD3 antibodies. Anti-CD3 stimulation induced large amounts of IFN-γ secretion from LN cells in both groups of mice. However, as shown in Fig. 3, LN cells from IRF-1−/− mice secreted a reduced amount of IFN-γ in response to dCII as compared with IRF-1+/− mice on day 14. On day 21, IFN-γ production in response to dCII was decreased in IRF-1+/− mice, while it remained at low levels in IRF-1−/− mice. These results suggest that IFN-γ production by LN cells in response to dCII is defective in IRF-1−/− mice.

Bottom Line: Interferon regulatory factor-1 (IRF-1) is a transcription factor that regulates interferon-induced genes and type I interferons.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.Expression of iNOS was also detected in inflamed spinal cords.

View Article: PubMed Central - PubMed

Affiliation: Amgen Institute, Department of Medical Biophysics, University of Toronto, Ontario, Canada.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus