IFN-gamma

IFN-gamma

Interferon-gamma (IFN-γ) is a critical cytokine in the immune system, playing a pivotal role in the regulation of immune responses. It is a type II interferon, distinct from type I interferons such as IFN-α and IFN-β. IFN-γ is primarily produced by natural killer (NK) cells and T lymphocytes, particularly CD4+ T helper 1 (Th1) cells and CD8+ cytotoxic T cells, upon activation by antigens or mitogens.

Structure and Function

IFN-γ is a dimeric protein composed of two identical subunits. It binds to the IFN-γ receptor, which is a heterodimer consisting of IFNGR1 and IFNGR2 subunits. Upon binding, the receptor activates the JAK-STAT signaling pathway, leading to the transcription of IFN-γ-responsive genes.

The primary functions of IFN-γ include:

• Activation of Macrophages: IFN-γ is a potent activator of macrophages, enhancing their microbicidal activity. It increases the expression of major histocompatibility complex (MHC) molecules, thereby improving antigen presentation.
• Promotion of Th1 Responses: IFN-γ promotes the differentiation of naive T cells into Th1 cells, which are essential for cell-mediated immunity against intracellular pathogens such as viruses and certain bacteria.
• Inhibition of Th2 Responses: By inhibiting Th2 cell differentiation, IFN-γ helps to modulate the immune response, preventing excessive antibody production and allergic reactions.
• Antiviral and Antitumor Activity: IFN-γ has direct antiviral effects and can inhibit the proliferation of tumor cells by inducing apoptosis and enhancing the immune system's ability to recognize and destroy cancer cells.

Clinical Significance

IFN-γ plays a crucial role in the immune response to infections and cancer. However, dysregulation of IFN-γ production or signaling can lead to various diseases:

• Autoimmune Diseases: Overproduction of IFN-γ is associated with autoimmune diseases such as rheumatoid arthritis and multiple sclerosis, where it contributes to tissue damage.
• Chronic Infections: In chronic infections like tuberculosis, IFN-γ is essential for controlling the infection, but excessive production can lead to tissue damage and fibrosis.
• Immunodeficiency: Genetic defects in the IFN-γ receptor can lead to increased susceptibility to mycobacterial infections, as seen in Mendelian susceptibility to mycobacterial disease (MSMD).

Therapeutic Applications

Recombinant IFN-γ is used therapeutically in certain conditions:

• Chronic Granulomatous Disease (CGD): IFN-γ is used to reduce the frequency of infections in patients with CGD, a genetic disorder affecting phagocyte function.
• Severe Malignant Osteopetrosis: IFN-γ can be used to improve immune function in patients with this rare bone disorder.

Also see

• Cytokine
• Interferon
• Immune system
• T helper cell
• Macrophage