negative regulation of type II interferon production

Definition

Target type: biologicalprocess

Any process that stops, prevents, or reduces the frequency, rate, or extent of interferon-gamma production. Interferon-gamma is also known as type II interferon. [GOC:add, GOC:mah, PMID:15546383]

Negative regulation of type II interferon (IFN-γ) production is a crucial mechanism for maintaining immune homeostasis and preventing excessive inflammation. It involves a complex interplay of signaling pathways, transcription factors, and regulatory molecules that act to suppress IFN-γ expression.

**1. Inhibition of IFN-γ Signaling:**

- **STAT1 phosphorylation:** Phosphorylation of STAT1, a key transcription factor involved in IFN-γ signaling, is inhibited by various mechanisms. For instance, suppressor of cytokine signaling (SOCS) proteins, particularly SOCS1 and SOCS3, can bind to and inhibit JAK kinases, the enzymes responsible for STAT1 phosphorylation.
- **Negative feedback loops:** IFN-γ itself can induce the expression of negative regulators, such as the inducible nitric oxide synthase (iNOS), which can suppress IFN-γ signaling.

**2. Inhibition of IFN-γ Transcription:**

- **Repression of IFN-γ gene expression:** Transcription factors like IRF-1 and T-bet are crucial for IFN-γ production. However, their activity can be suppressed by various mechanisms. For example, the transcription factor NF-κB, which is often activated in response to inflammation, can compete with IRF-1 for binding to the IFN-γ promoter.
- **Chromatin remodeling:** Histone deacetylation and methylation of the IFN-γ gene promoter can repress its accessibility to transcription factors, thus silencing IFN-γ expression.

**3. Immune Cell Regulation:**

- **Treg cell suppression:** Regulatory T cells (Tregs) play a vital role in suppressing immune responses. Tregs can suppress IFN-γ production by T helper 1 (Th1) cells, which are the main producers of IFN-γ. This suppression can be mediated through mechanisms such as CTLA-4-mediated inhibition of co-stimulatory signals and IL-10 production.
- **Regulatory cytokine production:** Cytokines like IL-10 and TGF-β, which are often produced by immune cells like macrophages and Tregs, can suppress IFN-γ production by inhibiting Th1 cell differentiation or directly suppressing IFN-γ transcription.

**4. Apoptosis of IFN-γ-producing cells:**

- Apoptosis (programmed cell death) of Th1 cells can decrease the number of cells producing IFN-γ, effectively reducing its overall levels. This can be triggered by factors like glucocorticoid hormones, which are known to induce apoptosis in immune cells.

**5. Viral Evasion Strategies:**

- Some viruses have evolved strategies to evade the host's immune system by suppressing IFN-γ production. For example, the Epstein-Barr virus (EBV) can interfere with the signaling pathways involved in IFN-γ production, making the host more susceptible to infection.

**Overall, negative regulation of IFN-γ production is a critical process that ensures proper immune function. It prevents excessive inflammation and autoimmunity, while also allowing for effective control of infections. Dysregulation of this process can lead to various immune disorders, highlighting its significance in maintaining immune homeostasis.**'
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Proteins (12)

Compounds (221)