negative regulation of type I interferon production

Definition

Target type: biologicalprocess

Any process that stops, prevents, or reduces the frequency, rate, or extent of type I interferon production. Type I interferons include the interferon-alpha, beta, delta, episilon, zeta, kappa, tau, and omega gene families. [GOC:add, GOC:mah]

Negative regulation of type I interferon (IFN) production is a crucial cellular process that prevents excessive and potentially harmful immune responses. This complex pathway involves a cascade of molecular interactions and signaling events aimed at tightly controlling the expression of IFN-alpha and IFN-beta, the primary cytokines responsible for triggering the antiviral and antitumor responses.

Here's a detailed overview of the key steps involved in this process:

**1. Sensing Viral or Pathogen-Associated Molecular Patterns (PAMPs):**
- Immune cells, such as macrophages, dendritic cells, and fibroblasts, possess pattern recognition receptors (PRRs) on their surfaces. These receptors recognize specific PAMPs associated with viruses, bacteria, or other pathogens.
- Examples of PRRs include Toll-like receptors (TLRs), retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), and cyclic GMP-AMP synthase (cGAS).

**2. Activation of Signaling Cascades:**
- Upon binding to PAMPs, PRRs trigger intracellular signaling cascades that lead to the activation of transcription factors, primarily interferon regulatory factors (IRFs).
- For example, TLRs activate the MyD88-dependent pathway, which culminates in the activation of IRF7. RLRs activate the mitochondrial antiviral signaling (MAVS) pathway, leading to the activation of IRF3.

**3. Induction of IFN-alpha and IFN-beta Gene Expression:**
- Activated IRFs translocate to the nucleus and bind to specific promoter regions of the IFN-alpha and IFN-beta genes.
- This binding event initiates the transcription of these genes, ultimately leading to the production of IFN-alpha and IFN-beta proteins.

**4. Negative Feedback Regulation:**
- IFN-alpha and IFN-beta, once produced, act in an autocrine and paracrine manner to induce the expression of a variety of antiviral and immune-modulatory genes.
- Importantly, they also trigger a series of negative feedback mechanisms to limit their own production.
- These mechanisms include the induction of suppressors of cytokine signaling (SOCS) proteins, which inhibit signaling pathways activated by PRRs.
- IFN-alpha and IFN-beta also induce the expression of A20, an ubiquitin ligase that negatively regulates the NF-kappaB pathway, a key transcription factor involved in the production of pro-inflammatory cytokines.

**5. Inhibition of Viral Replication and Immune Cell Activation:**
- The negative regulation of IFN-alpha and IFN-beta production ensures a balanced immune response, preventing excessive inflammation and tissue damage.
- This controlled production of IFN-alpha and IFN-beta allows for the effective inhibition of viral replication and the activation of immune cells to combat infection while limiting potential side effects.

**In summary, negative regulation of type I interferon production is a complex process involving a balance between activation and inhibition of signaling pathways. This intricate system ensures a controlled immune response, preventing excessive inflammation and promoting a successful defense against invading pathogens.**'
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Proteins (2)

Compounds (35)