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Gamma interferon: From antimicrobial activity to immune regulation

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Gamma interferon (IFNγ), a type II IFN, was discovered approximately seven years after discovery of type I IFNs. IFNs are defined as antiviral proteins, so the initial focus on IFNγ was directed toward its antiviral properties. Type I IFNs were shown to regulate antibody production in the early 1970’s, ...

Gamma interferon (IFNγ), a type II IFN, was discovered approximately seven years after discovery of type I IFNs. IFNs are defined as antiviral proteins, so the initial focus on IFNγ was directed toward its antiviral properties. Type I IFNs were shown to regulate antibody production in the early 1970’s, which opened up the vista of immune regulation to IFNs, including IFNγ. In fact, IFNγ is produced by cells of the immune system following antigen or mitogen signaling. The reviews presented here will focus on the following areas of IFNγ:

1. IFNγ and signal transduction. The JAK/STAT signaling pathway dominates our view of specific gene activation by IFNγ. There are over 60 different cytokines, growth factors, and hormones that use the JAK/STAT pathway, and some use the same STAT transcription factors as IFNγ. Thus, IFNγ signaling will be addressed in the context of specificity-determining events.

2. IFNγ and lymphocytes phenotypes. T helper 1 cells are partially defined by their production of IFNγ. IFNγ is also produced by natural killer cells. The significance of cellular source of IFNγ will be addressed in the context of other lymphocyte phenotypes and autoimmune diseases that are linked to IFNγ.

3. Regulation of IFNγ. IFNγ plays the central role in lethal inflammatory neonatal disease that results from regulatory T cell or suppressor of cytokine signaling 1 (SOCS1) deficiency. How Tregs and SOCS1 regulate IFNγ function will be addressed.

4. IFNγ and host defense against infectious diseases and cancer. There is evidence that IFNγ plays an important role in host defense against infection by Mycobacterium tuberculosis as well as viral hepatitis. IFNγ is also considered to be important in defense against some forms of cancer. The challenge is how IFNγ can be used as a therapeutic in these infectious diseases and cancers.

5. IFNγ and the epigentics of gene activation. The usual measurements of DNA methylation/demethylation, histone methylation/demethylation, and histone acetylation involving specific residues such as lysine on histone H3 are seldom defined in the context of the specificity of IFNγ signaling. We will attempt to link IFNγ signal transduction epigenetics to specific gene activation including the nuclear role of activated JAKs.


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