Page last updated: 2024-10-24

mature conventional dendritic cell differentiation

Definition

Target type: biologicalprocess

The process in which antigen-activated dendritic cells acquire the specialized features of a mature conventional dendritic cell. Mature conventional dendritic cells upregulate the surface expression of MHC molecules, chemokine receptors and adhesion molecules, and increase the number of dendrites (cytoplasmic protrusions) in preparation for migration to lymphoid organs where they present antigen to T cells. [GOC:BHF, http://www.rndsystems.com/mini_review_detail_objectname_MR02_DendriticCellMat.aspx, PMID:15845453]

Mature conventional dendritic cells (cDCs) are specialized antigen-presenting cells (APCs) that play a critical role in initiating and shaping adaptive immune responses. Their differentiation from precursor cells is a complex and tightly regulated process involving a series of distinct stages characterized by specific molecular markers and functional properties.

The differentiation pathway of cDCs can be broadly divided into two main branches:
1) the conventional type 1 dendritic cell (cDC1) lineage and
2) the conventional type 2 dendritic cell (cDC2) lineage.

**cDC1 differentiation:**
cDC1 precursors originate from common lymphoid progenitors (CLPs) in the bone marrow. These precursors migrate to the thymus, where they undergo a series of developmental steps characterized by the sequential expression of transcription factors such as Notch, BATF3, and IRF8.

**cDC2 differentiation:**
cDC2 precursors originate from common myeloid progenitors (CMPs) in the bone marrow. They migrate to peripheral tissues where they differentiate into pre-cDC2s, and finally mature cDC2s. This process is regulated by factors such as flt3 ligand (FL), GM-CSF, and IL-4.

**Key features of mature cDCs:**
- **Antigen uptake:** cDCs are highly efficient at capturing antigens through phagocytosis, macropinocytosis, and receptor-mediated endocytosis.
- **Antigen processing:** cDCs internalize and process antigens, breaking them down into small peptides that can bind to MHC molecules.
- **MHC expression:** Mature cDCs express high levels of both MHC class I and MHC class II molecules, which are essential for antigen presentation to T cells.
- **Co-stimulatory molecule expression:** Mature cDCs express a range of co-stimulatory molecules, such as CD80, CD86, and CD40, which are required for T cell activation.
- **Cytokine production:** Mature cDCs produce a variety of cytokines, including IL-12, IL-6, and TNF-alpha, which can influence the differentiation and function of T cells.
- **Migration:** Mature cDCs migrate to lymph nodes, where they present antigens to T cells and initiate adaptive immune responses.

**Regulation of cDC differentiation:**
The differentiation of cDCs is tightly regulated by a complex network of signals, including:
- **Cytokines:** FL, GM-CSF, IL-4, IL-12, IL-15, and TGF-beta
- **Growth factors:** VEGF, FGF, and PDGF
- **Transcription factors:** BATF3, IRF4, IRF8, and PU.1
- **Microenvironment:** The presence of specific tissue environments, such as the thymus, lymph nodes, and skin, can influence cDC differentiation.

**The differentiation of mature cDCs is a dynamic process that is critical for the initiation and regulation of adaptive immune responses.**'"

Proteins (4)

ProteinDefinitionTaxonomy
Proteinase-activated receptor 2A proteinase-activated receptor 2 that is encoded in the genome of human. [PRO:WCB, UniProtKB:P55085]Homo sapiens (human)
C-C chemokine receptor type 7A C-C chemokine receptor type 7 that is encoded in the genome of human. [PRO:WCB, UniProtKB:P32248]Homo sapiens (human)
MyeloblastinA myeloblastin that is encoded in the genome of human. [PRO:DNx, UniProtKB:P24158]Homo sapiens (human)
Galectin-9A galectin-9 that is encoded in the genome of human. [PRO:DNx, UniProtKB:O00182]Homo sapiens (human)

Compounds (15)

CompoundDefinitionClassesRoles
phenylmethylsulfonyl fluoridephenylmethanesulfonyl fluoride : An acyl fluoride with phenylmethanesulfonyl as the acyl group.

Phenylmethylsulfonyl Fluoride: An enzyme inhibitor that inactivates IRC-50 arvin, subtilisin, and the fatty acid synthetase complex.
acyl fluorideserine proteinase inhibitor
lactosebeta-lactose : The beta-anomer of lactose.

lactose : A glycosylglucose disaccharide, found most notably in milk, that consists of D-galactose and D-glucose fragments bonded through a beta-1->4 glycosidic linkage. The glucose fragment can be in either the alpha- or beta-pyranose form, whereas the galactose fragment can only have the beta-pyranose form.

Lactose: A disaccharide of GLUCOSE and GALACTOSE in human and cow milk. It is used in pharmacy for tablets, in medicine as a nutrient, and in industry.
lactose
methyl alpha-d-galactopyranosidemethyl alpha-D-galactoside : An alpha-D-galactoside having a methyl substituent at the anomeric position.

methyl-galactopyranoside: structure in first source
alpha-D-galactoside;
methyl D-galactoside;
monosaccharide derivative
methyl beta-galactosidemethyl beta-D-galactoside : A beta-D-galactopyranoside having a methyl substituent at the anomeric position.

methyl beta-galactoside: RN given refers to (beta-D)-isomer

methyl galactoside : A methyl glycoside in which the H of the OH group on C-1 of galactose is replaced by a methyl group.
beta-D-galactoside;
methyl D-galactoside;
monosaccharide derivative
sivelestatsivelestat: inhibitor of neutrophil elastase; structure given in first sourceN-acylglycine;
pivalate ester
triptolidediterpenoid;
epoxide;
gamma-lactam;
organic heteroheptacyclic compound
antispermatogenic agent;
plant metabolite
thiodigalactosidethiodigalactoside: RN given refers to beta-D-galactopyranoside (D-Gal)-isomer
methyl lactosidebeta-D-Gal-(1->4)-beta-D-Glc-OMe : A methyl glycoside comprising methyl beta-D-glucoside having an beta-D-galactosyl residue at the 4-position.disaccharide derivative;
methyl glycoside
tak 779
n-acetyllactosamineN-acetyllactosamine : A beta-D-galactopyranosyl-(1->4)-N-acetyl-D-glucosamine having beta-configuration at the reducing end anomeric centre.

N-acetyllactosamine: RN given refers to D-isomer
beta-D-Galp-(1->4)-D-GlcpNAc
galactalgalactal: RN given refers to cpd with unspecified isomeric designation; structureanhydrohexose;
glycal
seryl-leucyl-isoleucyl-glycyl--arginyl-leucinamideseryl-leucyl-isoleucyl-glycyl--arginyl-leucinamide: a proteinase-activated receptor-2-activating peptide; SL-NH2 is NOT Ser-Leu-NH2 here
2-furoyl-ligrlo-amide2-furoyl-LIGRLO-amide: a potent and selective proteinase-activated receptor 2 agonist
cenicriviroccenicriviroc : A member of the class of benzazocines that is (5Z)-1,2,3,4-tetrahydro-1-benzazocine which is substituted by a 2-methylpropyl, N-{4-[(S)-(1-propyl-1H-imidazol-5-yl)methanesulfinyl]phenyl}carboxamide and 4-(2-butoxyethoxy)phenyl groups at positions 1, 5 and 8, respectively. It is a potent chemokine 2 and 5 receptor antagonist currently in development for the treatment of liver fibrosis in adults with nonalcoholic steatohepatitis (NASH).

cenicriviroc: an inhibitor of HIV-1
aromatic ether;
benzazocine;
diether;
imidazoles;
secondary carboxamide;
sulfoxide
anti-HIV agent;
anti-inflammatory agent;
antirheumatic drug;
chemokine receptor 2 antagonist;
chemokine receptor 5 antagonist
AZ3451benzimidazoles;
benzodioxoles;
nitrile;
organobromine compound;
secondary carboxamide
anti-inflammatory agent;
autophagy inducer;
PAR2 negative allosteric modulator