negative regulation of natural killer cell mediated cytotoxicity

Definition

Target type: biologicalprocess

Any process that stops, prevents, or reduces the rate of natural killer mediated cytotoxicity. [GOC:add, ISBN:0781735149]

Negative regulation of natural killer (NK) cell mediated cytotoxicity is a complex process that involves a variety of mechanisms designed to prevent NK cells from killing healthy cells. This process is essential for maintaining immune homeostasis and preventing autoimmunity. Here are some of the key mechanisms involved:

1. **Inhibitory receptors:** NK cells express a variety of inhibitory receptors that bind to specific ligands expressed on healthy cells. These receptors deliver signals that suppress NK cell activation and cytotoxicity. Some of the important inhibitory receptors include:
* **KIRs (Killer cell immunoglobulin-like receptors):** These receptors recognize MHC class I molecules expressed on healthy cells. When KIRs bind to their ligands, they send inhibitory signals to the NK cell, preventing activation.
* **PD-1 (Programmed Death 1):** This receptor binds to PD-L1 and PD-L2 ligands expressed on target cells, sending inhibitory signals to the NK cell.
* **CTLA-4 (Cytotoxic T-lymphocyte-associated protein 4):** While primarily known for its role in T cells, CTLA-4 can also be expressed on NK cells and inhibit their function.
* **TIGIT (T cell immunoglobulin and ITIM domain):** TIGIT binds to CD155 and CD112, which are expressed on various cells, including target cells. Binding of TIGIT to its ligands inhibits NK cell function.

2. **MHC Class I expression:** MHC class I molecules are expressed on the surface of most cells and serve as markers of self. NK cells recognize a lack of MHC class I molecules, which is often a sign of a cancerous or infected cell. However, healthy cells express MHC class I molecules to inhibit NK cell activation. If a cell loses its MHC class I expression, it becomes susceptible to NK cell killing.

3. **Cytokine modulation:** The cytokine environment plays a crucial role in regulating NK cell activity. For example, the cytokines IL-10 and TGF-beta can suppress NK cell cytotoxicity. These cytokines are often produced by cells in response to an immune response, acting as a "brake" to control the intensity of the immune response.

4. **Apoptosis of NK cells:** In some cases, NK cells may be induced to undergo apoptosis (programmed cell death). This can be triggered by various factors, such as prolonged activation or exposure to inhibitory signals. Apoptosis of NK cells can help to prevent excessive immune responses.

5. **Other factors:** Additional factors can influence NK cell regulation, including the expression of inhibitory molecules on target cells, the presence of specific cell types in the microenvironment, and the presence of specific chemokines.

**Overall, negative regulation of NK cell mediated cytotoxicity is a critical component of the immune system. It ensures that NK cells target only the appropriate cells, preventing self-damage and maintaining immune homeostasis.**'
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Proteins (1)

Compounds (7)