regulatory T cell apoptotic process

Definition

Target type: biologicalprocess

Any apoptotic process in a regulatory T cell. [GOC:nhn, GOC:TermGenie, PMID:20471291]

Regulatory T cells (Tregs) play a crucial role in maintaining immune homeostasis by suppressing autoreactive T cells and regulating inflammatory responses. Apoptosis, a form of programmed cell death, is a tightly regulated process that eliminates unwanted or damaged cells. In the context of Tregs, apoptosis can be induced by various stimuli, including:

- **Activation-induced cell death (AICD):** Excessive TCR stimulation, often triggered by prolonged exposure to antigens, can lead to the activation of pro-apoptotic pathways within Tregs. This process involves the upregulation of Fas ligand (FasL) and the expression of pro-apoptotic proteins like caspase-8 and caspase-3.

- **Cytokine-mediated apoptosis:** Tregs can be induced to undergo apoptosis by certain cytokines, such as TNF-α and IFN-γ. These cytokines can activate signaling pathways that promote the expression of pro-apoptotic proteins.

- **Mitochondrial-mediated apoptosis:** Stressful conditions, including nutrient deprivation or DNA damage, can trigger the release of cytochrome c from mitochondria into the cytoplasm. Cytochrome c activates caspase-9, which further activates the caspase cascade, leading to apoptosis.

- **Granzyme-mediated apoptosis:** Cytotoxic T lymphocytes (CTLs) can directly induce apoptosis in Tregs by releasing granzyme B, a serine protease that enters the target cell and activates caspase-3.

- **Fas-FasL pathway:** Engagement of the Fas receptor (Fas) on Tregs by its ligand (FasL) initiates a signaling cascade that activates caspase-8, ultimately leading to apoptosis. This pathway is important in controlling the number and activity of Tregs.

**Consequences of Treg Apoptosis:**

- **Loss of immune suppression:** The death of Tregs can disrupt immune tolerance and lead to the development of autoimmune diseases.
- **Uncontrolled inflammation:** Without Tregs to suppress inflammatory responses, immune cells can attack healthy tissues, causing tissue damage and disease.
- **Increased susceptibility to infection:** Tregs contribute to immune homeostasis by suppressing immune responses to commensal bacteria and other harmless antigens. Their loss can increase susceptibility to infections.

**Regulation of Treg Apoptosis:**

- **Anti-apoptotic factors:** Tregs express anti-apoptotic proteins like Bcl-2 and Bcl-xL, which inhibit the activation of the caspase cascade and promote cell survival.
- **Survival signals:** Cytokines such as IL-2 and TGF-β can provide survival signals to Tregs, preventing them from undergoing apoptosis.
- **Microenvironment:** The microenvironment surrounding Tregs can influence their survival. For instance, the presence of specific chemokines and growth factors can promote Treg survival and function.'
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Compounds (4)