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)

Compounds (15)