negative regulation of leukocyte proliferation

Definition

Target type: biologicalprocess

Any process that stops, prevents, or reduces the frequency, rate or extent of leukocyte proliferation. [GOC:add, GOC:mah]

Negative regulation of leukocyte proliferation is a complex process involving various cellular and molecular mechanisms that restrain the growth and division of leukocytes, ultimately preventing uncontrolled immune responses and maintaining immune homeostasis. This process is crucial for preventing excessive inflammation, autoimmune disorders, and the development of leukemia.

Key mechanisms involved in negative regulation of leukocyte proliferation include:

1. **Cytokine signaling:**
* **TGF-beta:** A potent immunosuppressive cytokine that inhibits the proliferation of various leukocyte populations, including T cells, B cells, and NK cells. It achieves this by activating signaling pathways that induce cell cycle arrest and promote apoptosis.
* **IL-10:** Another immunosuppressive cytokine that primarily targets activated T cells, reducing their proliferation and cytokine production. IL-10 exerts its effect by inhibiting the expression of pro-inflammatory cytokines and promoting the differentiation of regulatory T cells.
* **IL-12:** While primarily known for its pro-inflammatory role, IL-12 also contributes to negative regulation by promoting the differentiation of regulatory T cells, which suppress the proliferation of other T cells.

2. **Apoptosis:** Programmed cell death is a critical mechanism for eliminating activated leukocytes after an immune response. It is triggered by various factors, including cytokine withdrawal, DNA damage, and activation of death receptors.

3. **Immune checkpoint molecules:** These proteins expressed on immune cells act as brakes to prevent excessive activation.
* **CTLA-4:** A receptor expressed on T cells that binds to the same ligands as CD28, a costimulatory molecule. By competing with CD28, CTLA-4 inhibits T cell activation and proliferation.
* **PD-1:** Another inhibitory receptor expressed on T cells, which interacts with PD-L1 and PD-L2 ligands on antigen-presenting cells. PD-1 signaling suppresses T cell activation and proliferation.

4. **Regulatory T cells (Tregs):** These specialized T cell subsets actively suppress the proliferation of other immune cells, maintaining immune tolerance and preventing autoimmunity. Tregs accomplish this through various mechanisms, including the production of immunosuppressive cytokines like IL-10 and TGF-beta, and the expression of inhibitory molecules like CTLA-4.

5. **Other mechanisms:**
* **Hypoxia:** Low oxygen levels in the tumor microenvironment can suppress leukocyte proliferation and activation, contributing to immune evasion by cancer cells.
* **Metabolic reprogramming:** Leukocytes require specific metabolic pathways for proliferation and activation. Inhibiting these pathways can effectively reduce leukocyte growth.

Overall, negative regulation of leukocyte proliferation is a complex and multi-faceted process that involves a delicate balance of positive and negative signals. Disruptions in this regulatory network can lead to various pathological conditions, highlighting the crucial role of these mechanisms in maintaining immune homeostasis.'
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Proteins (1)

Compounds (10)