A Murine Model of Inflammation Based on Chronic Expression of Interferon-Gamma

An autoimmune disease is characterized by a malfunctioning healthy immune system mistakenly attacking healthy cells, tissues, and organs. These chronic diseases likely result from interactions between genetic and environmental factors. Gender, race, and ethnicity characteristics have been linked to the development of an autoimmune disease. Autoimmune diseases affect approximately 8% of the population, 78% of whom are women. Importantly, autoimmunity is known to have a genetic basis and tends to cluster in families.The cytokine Interferon gamma (IFN γ) is critical for innate and adaptive immune responses. Aberrant expression of this pro-inflammatory factor is linked to several autoimmune and autoinflammatory diseases. Its importance in the immune system stems from its immunostimulatory and immunomodulatory effects and the ability to inhibit vi ral replication directly. IFNγ is also essential many immunotherapies to be successful. Several instances of signaling modulation seem particularly applicable to autoimmune inflammation.The lab of Dr. Howard Young at NCI ’s Laboratory of Cancer Immunometabolism developed an ARE-Del mouse model for studying female-biased autoimmune diseases. By replacing the sequence that enhances IFNγ mRNA degradation (AU Rich Elements) with random nucleotides, these mice produce stable IFNγ mRNA in T-cells and NK cells and chro nic protein expression in the serum. This model enables both short- and long-term assessment of the effects of IFNγ on h...
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