dendritic cell apoptotic process

Definition

Target type: biologicalprocess

Any apoptotic process in a dendritic cell, a cell of hematopoietic origin, typically resident in particular tissues, specialized in the uptake, processing, and transport of antigens to lymph nodes for the purpose of stimulating an immune response via T cell activation. [CL:0000451, GOC:BHF, GOC:mtg_apoptosis, PMID:15059845]

Dendritic cells (DCs) are specialized antigen-presenting cells that play a critical role in initiating and regulating immune responses. Apoptotic DCs can arise from various physiological and pathological processes, and their fate and function can significantly impact the immune system.

The process of dendritic cell apoptosis is a complex and tightly regulated event involving multiple signaling pathways and molecular mechanisms. It is generally triggered by a variety of stimuli, including:

**1. Extrinsic Pathways:**
* **Fas ligand (FasL) and TNF-alpha:** These death receptors are expressed on lymphocytes and other immune cells, and their binding to Fas or TNF-alpha on DCs initiates the extrinsic apoptotic pathway. This pathway involves the activation of caspase-8, which then activates downstream caspases, leading to the execution of apoptosis.

**2. Intrinsic Pathways:**
* **Mitochondrial dysfunction:** Various cellular stresses, such as DNA damage, oxidative stress, and growth factor deprivation, can lead to mitochondrial membrane permeabilization and the release of cytochrome c into the cytosol. Cytochrome c then activates caspase-9, which triggers the apoptotic cascade.
* **ER stress:** Accumulation of misfolded proteins in the endoplasmic reticulum (ER) can activate the unfolded protein response (UPR), which can induce apoptosis in DCs.

**3. Other Pathways:**
* **Granzyme B:** This serine protease, released by cytotoxic T lymphocytes (CTLs), can directly enter DCs and activate caspases, leading to apoptosis.

**4. Autophagy:** Autophagy is a cellular process involved in the degradation and recycling of cellular components. While it can promote cell survival under certain conditions, autophagy can also contribute to apoptosis in DCs, especially when it becomes excessive or dysregulated.

**Apoptotic DCs undergo characteristic morphological and biochemical changes, including:**

* **Cell shrinkage and membrane blebbing:** The apoptotic cell shrinks, and its membrane develops blebs, small protrusions that can detach and form apoptotic bodies.
* **Nuclear fragmentation:** The nucleus of the apoptotic cell condenses and breaks down into fragments, known as apoptotic bodies.
* **DNA cleavage:** DNA is cleaved by caspase-activated DNases, known as CADs, into fragments of specific sizes, which can be detected by DNA fragmentation assays.
* **Exposure of phosphatidylserine on the outer leaflet of the plasma membrane:** This lipid normally resides on the inner leaflet of the plasma membrane, but it is exposed on the outer leaflet during apoptosis. This acts as a signal for phagocytes to engulf the apoptotic cell.

**Fate of Apoptotic DCs:**

* **Phagocytosis by macrophages and other immune cells:** Phagocytosis of apoptotic DCs by macrophages is crucial for the removal of cellular debris and the prevention of inflammation. It also allows the transfer of antigens from apoptotic DCs to phagocytes, which can then present them to T cells.
* **Induction of tolerogenic responses:** Apoptotic DCs can induce tolerogenic responses in T cells, which can prevent autoimmune reactions and maintain immune homeostasis.
* **Release of exosomes:** Apoptotic DCs can release exosomes, small vesicles containing various molecules, including antigens and signaling molecules. These exosomes can influence the function of other cells and contribute to the spread of immune responses.

**Importance of Dendritic Cell Apoptosis in Immune Regulation:**

* **Immune tolerance:** Apoptotic DCs play a crucial role in inducing immune tolerance by presenting antigens to T cells in a non-inflammatory context.
* **Control of inflammation:** Phagocytosis of apoptotic DCs by macrophages helps to resolve inflammation and maintain immune homeostasis.
* **Anti-tumor immunity:** Apoptotic DCs can stimulate anti-tumor immunity by presenting tumor antigens to T cells.

**Disruptions in Dendritic Cell Apoptosis:**

* **Defective apoptosis:** Impaired apoptosis in DCs can contribute to chronic inflammation, autoimmune diseases, and cancer.
* **Excessive apoptosis:** Excessive apoptosis of DCs can suppress immune responses and increase susceptibility to infections.

Understanding the process of dendritic cell apoptosis is essential for developing strategies to manipulate immune responses in various diseases, such as cancer, autoimmunity, and infectious diseases.'
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