Interferon-γ in foam cell formation and progression of atherosclerosis

Interferon-γ (IFN-γ), the sole member in type II IFN predominantly secreted by macrophages and T cells, is a critical regulator of immune function and provides a robust first line of defense against invading pathogens. Binding of IFN-γ to its receptor complex can activate a variety of downstream signaling pathways, particularly the Janus kinase (JAK)/signal transducer and activator of transcription (STAT), to induce gene transcription within the target cells. This pro-inflammatory mediator is highly expressed in atherosclerotic lesions and promotes foam cell formation, but its effects on the atherogenesis are complex, with both pro- and anti-atherogenic properties. IFN-γ also contributes to the development of myocardial infarction and stroke, the two main atherosclerotic diseases. Inhibition of IFN-γ signaling may prevent the development of atherosclerosis and help treat atherosclerotic diseases. Since IFN-γ may also exert anti-atherogenic effects, the safety and efficacy of anti-IFN-γ treatment still require careful evaluation in the clinical setting. In the current review, we summarize recent progression on regulation and signaling pathways of IFN-γ, and highlight its roles in foam cell formation, atherosclerosis, myocardial infarction as well as stroke. An increased understanding of these processes will help to develop novel IFN-γ-centered therapies for atherosclerotic diseases.