Page last updated: 2024-10-24

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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Proteins (2)

ProteinDefinitionTaxonomy
Bcl-2-like protein 1A Bcl-2-like protein 1 that is encoded in the genome of human. [PRO:WCB, UniProtKB:Q07817]Homo sapiens (human)
Apoptosis regulator Bcl-2An apoptosis regulator Bcl-2 that is encoded in the genome of human. [PRO:WCB, UniProtKB:P10415]Homo sapiens (human)

Compounds (46)

CompoundDefinitionClassesRoles
oxamic acidoxamic acid : A dicarboxylic acid monoamide resulting from the formal condensation of one of the carboxy groups of oxalic acid with ammonia.

Oxamic Acid: Amino-substituted glyoxylic acid derivative.
dicarboxylic acid monoamideEscherichia coli metabolite
catechinhydroxyflavan
hoe 33342BXI-72: structure in first sourcebibenzimidazole;
N-methylpiperazine
fluorochrome
chelerythrinechelerythrine : A benzophenanthridine alkaloid isolated from the root of Zanthoxylum simulans, Chelidonium majus L., and other Papaveraceae.benzophenanthridine alkaloid;
organic cation
antibacterial agent;
antineoplastic agent;
EC 2.7.11.13 (protein kinase C) inhibitor
chlorcyclizinechlorcyclizine: was heading 1964-94 (Prov 1964-73); CHLOROCYCLIZINE & HISTACHLORAZINE were see CHLORCYCLIZINE 1977-94; use PIPERAZINES to search CHLORCYCLIZINE 1966-94; histamine H1-blocker used both orally and topically in allergies and also for the prevention of motion sicknessdiarylmethane
gossypolGossypol: A dimeric sesquiterpene found in cottonseed (GOSSYPIUM). The (-) isomer is active as a male contraceptive (CONTRACEPTIVE AGENTS, MALE) whereas toxic symptoms are associated with the (+) isomer.
sanguinarinebenzophenanthridine alkaloid : A specific group of isoquinoline alkaloids that occur only in higher plants and are constituents mainly of the Papaveraceae family.alkaloid antibiotic;
benzophenanthridine alkaloid;
botanical anti-fungal agent
alizarindihydroxyanthraquinonechromophore;
dye;
plant metabolite
2-phenylphenol2-phenylphenol: RN given refers to parent cpd; structure

biphenyl-2-ol : A member of the class of hydroxybiphenyls that is biphenyl substituted by a hydroxy group at position 2. It is generally used as a post-harvest fungicide for citrus fruits.
hydroxybiphenylsantifungal agrochemical;
environmental food contaminant
4-phenylphenol4-phenylphenol: RN given refers to cpd without isomeric designation

biphenyl-4-ol : A member of the class of hydroxybiphenyls that is biphenyl carrying a hydroxy group at position 4.
hydroxybiphenyls
paclitaxelTaxus: Genus of coniferous yew trees or shrubs, several species of which have medicinal uses. Notable is the Pacific yew, Taxus brevifolia, which is used to make the anti-neoplastic drug taxol (PACLITAXEL).taxane diterpenoid;
tetracyclic diterpenoid
antineoplastic agent;
human metabolite;
metabolite;
microtubule-stabilising agent
epigallocatechin gallate(-)-epigallocatechin 3-gallate : A gallate ester obtained by the formal condensation of gallic acid with the (3R)-hydroxy group of (-)-epigallocatechin.

epigallocatechin gallate: a steroid 5alpha-reductase inhibitor and antimutagen in green tea (Camellia sinensis)
flavans;
gallate ester;
polyphenol
antineoplastic agent;
antioxidant;
apoptosis inducer;
geroprotector;
Hsp90 inhibitor;
neuroprotective agent;
plant metabolite
5,6,7,8-tetrahydro-1-naphthol5,6,7,8-tetrahydro-1-naphthol : 1-naphthol hydrogenated at C-5, -6, -7 and -8.tetralins
epicatechin(-)-epicatechin : A catechin with (2R,3R)-configuration.catechin;
polyphenol
antioxidant
gallocatechol(-)-epigallocatechin : A flavan-3,3',4',5,5',7-hexol having (2R,3R)-configuration.catechin;
flavan-3,3',4',5,5',7-hexol
antioxidant;
food component;
plant metabolite
chelerythrine chloride
benzo(b)thiophene-2-carboxylic acidbenzo(b)thiophene-2-carboxylic acid: for prevention of osteoporosis; structure given in first source
alexidine dihydrchloride
epicatechin gallate(-)-epicatechin-3-O-gallate : A gallate ester obtained by formal condensation of the carboxy group of gallic acid with the (3R)-hydroxy group of epicatechin. A natural product found in Parapiptadenia rigida.

epicatechin gallate: a steroid 5alpha-reductase inhibitor; RN given refers to the (cis)-isomer; structure given in first source; isolated from green tea
catechin;
gallate ester;
polyphenol
EC 3.2.1.1 (alpha-amylase) inhibitor;
EC 3.2.1.20 (alpha-glucosidase) inhibitor;
metabolite
6-n-tridecylsalicylic acid6-n-tridecylsalicylic acid: structure given in first sourcehydroxybenzoic acid
blastmycinblastmycin: structureamidobenzoic acid
resveratroltrans-resveratrol : A resveratrol in which the double bond has E configuration.resveratrolantioxidant;
phytoalexin;
plant metabolite;
quorum sensing inhibitor;
radical scavenger
apogossypolapogossypol: structure in first source
umi-77UMI-77: an Mcl-1 inhibitor; structure in first source
4-(4-ethoxycarbonylanilino)-2-quinazolinecarboxylic acid ethyl esterquinazolines
thioguanine anhydrousThioguanine: An antineoplastic compound which also has antimetabolite action. The drug is used in the therapy of acute leukemia.

tioguanine : A 2-aminopurine that is the 6-thiono derivative of 2-amino-1,9-dihydro-6H-purine. Incorporates into DNA and inhibits synthesis. Used in the treatment of leukaemia.
2-aminopurinesanticoronaviral agent;
antimetabolite;
antineoplastic agent
5,6-dehydrokawain5,6-dehydrokawain: from Alpinia speciosa rhizoma; RN given for cpd without isomeric designation; structure given in first source2-pyranones;
aromatic ether
kendomycinkendomycin: structure in first sourcebenzofurans
rehmannic acidrehmannic acid: toxic principle, triterpene acid from Lantana camara; RN given refers to (22beta-(Z))-isomer; structure
ixabepilone1,3-thiazoles;
beta-hydroxy ketone;
epoxide;
lactam;
macrocycle
antineoplastic agent;
microtubule-destabilising agent
abt-737aromatic amine;
aryl sulfide;
biphenyls;
C-nitro compound;
monochlorobenzenes;
N-arylpiperazine;
N-sulfonylcarboxamide;
secondary amino compound;
tertiary amino compound
anti-allergic agent;
anti-inflammatory agent;
antineoplastic agent;
apoptosis inducer;
B-cell lymphoma 2 inhibitor
nutlin-3anutlin 3: an MDM2 antagonist; structure in first sourcestilbenoid
N-[4-(2-tert-butylphenyl)sulfonylphenyl]-2,3,4-trihydroxy-5-[(2-propan-2-ylphenyl)methyl]benzamidebenzamides
MI-63MI-63 : An azaspiro compound resulting from the formal fusion of position 3 of 6-chloro-oxindole with position 3 of (2R,3SS5S)-3-(3-chloro-2-fluorophenyl)-5-(2,2-dimethylpropyl)-N-[2-(morpholin-4-yl)ethyl]pyrrolidine-2-carboxamide. It is a potent inhibitor of the MDM2-p53 interaction.azaspiro compound;
monochlorobenzenes;
monofluorobenzenes;
morpholines;
oxindoles;
pyrrolidines;
secondary carboxamide
apoptosis inducer
marinopyrrole a(-)-marinopyrrole A : A member of the class of pyrroles that is 1'H-1,3'-bipyrrole substituted by four chloro groups at positions 4, 4', 5 and 5' and two 2-hydroxybenzoyl moieties at positions 2 and 2'. It is isolated from Streptomyces sp.CNQ-418 and exhibits cytotoxic and antibacterial activities.

marinopyrrole A: antibiotic from a marine Streptomyces sp.; structure in first source
aromatic ketone;
organochlorine compound;
phenols;
pyrroles
antibacterial agent;
antimicrobial agent;
antineoplastic agent;
bacterial metabolite;
marine metabolite
navitoclaxaryl sulfide;
monochlorobenzenes;
morpholines;
N-sulfonylcarboxamide;
organofluorine compound;
piperazines;
secondary amino compound;
sulfone;
tertiary amino compound
antineoplastic agent;
apoptosis inducer;
B-cell lymphoma 2 inhibitor
ethyl 2-amino-6-(3,5-dimethoxyphenyl)-4-(2-ethoxy-2-oxoethyl)-4h-chromene-3-carboxylateethyl 2-amino-6-(3,5-dimethoxyphenyl)-4-(2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate: has antineoplastic activity; structure in first source
meiogynin ameiogynin A: from the bark of Meiogyne cylindrocarpa; structure in first source
abt-199venetoclax : A member of the class of pyrrolopyridines that is a potent inhibitor of the antiapoptotic protein B-cell lymphoma 2. It is used for treamtment of chronic lymphocytic leukemia with 17p deletion.

venetoclax: A BCL-2 inhibitor with antineoplastic activity that is used in the treatment of CHRONIC LYMPHOCYTIC LEUKEMIA associated with chromosome 17p deletion; structure in first source.
aromatic ether;
C-nitro compound;
monochlorobenzenes;
N-alkylpiperazine;
N-arylpiperazine;
N-sulfonylcarboxamide;
oxanes;
pyrrolopyridine
antineoplastic agent;
apoptosis inducer;
B-cell lymphoma 2 inhibitor
nvp-cgm097NVP-CGM097: an MDM2 and HDM2 inhibitor; structure in first source
jy-1-106JY-1-106: a BH3 alpha-helix mimetic that functions as a pan-Bcl-2 inhibitor; structure in first source
a-1155463A-1155463: a Bcl-X(L) inhibitor; structure in first source
bm-1197BM-1197: inhibits both Bcl-xL and Bcl-2; has antineoplastic activity
a-1331852A-1331852: a Bcl-X(L) inhibitor; structure in first source
BDA-366BDA-366 : A member of the class of anthraquinone that is 1,4-diamino-9,10-anthraquinone in which the two amino groups are carrying 3-(diethylamino)-2-hydroxypropyl and (oxiran-2-yl)methyl substituents. It exhibits anti-cancer properties.

BDA-366: has antineoplastic activity; binds Bcl-2 protein; structure in first source
anthraquinone;
epoxide;
secondary alcohol;
secondary amino compound;
tertiary amino compound
antineoplastic agent;
apoptosis inducer
apogossypoloneapogossypolone: has antineoplastic activity; structure in first source