Fundamental properties
A dendritic (branched) shape can also be found in other cells (e.g., certain skin T lymphocytes). For a cell to be reliably classified as a dendritic cell, it must possess a classic combination of three features:
- Specific morphology: in tissues they have a tree-like shape, while in the bloodstream and cell cultures they form prominent pseudopodia and microvilli (which is why they are often called "veiled cells").
- Phenotypic features: high expression of MHC (major histocompatibility complex) molecules of not only class I, but also class II is detected on the membrane. This is combined with the presence of costimulatory molecules CD80 and CD86.
- Functional activity: they specialize in antigen capture (predominantly via pinocytosis and less frequently phagocytosis). After antigen processing, the cell presents it to T lymphocytes, causing their activation.
Origin and histogenesis
All dendritic cells develop from hematopoietic stem cells of the bone marrow, but their maturation can follow two different pathways:
- Myeloid lineage: the majority of the body's dendritic cells. They develop from a common granulocyte-monocyte progenitor or directly from monocytes.
- Lymphoid lineage: differentiate from a common lymphoid progenitor (sometimes even from the earliest thymocytes — DN1 cells).
An important distinguishing feature of all dendritic cell progenitors is the presence of the FLT-3 (Fms-like tyrosine kinase 3) cytokine receptor on the membrane. In the bloodstream, cells are at intermediate stages of development before migrating into tissues.
Life cycle, maturation and migration
Immature dendritic cells settle in barrier tissues (skin, mucous membranes), where they intensively uptake surrounding material. As soon as a cell encounters a pathogen (via pattern-recognition receptors) or pro-inflammatory cytokines, it is activated and begins to move along with tissue fluid into lymphatic vessels, and then into regional lymph nodes.
During this migration, DC maturation takes place:
- The capacity for active endocytosis drops sharply.
- Peptide fragments of the captured protein are integrated into MHC molecules.
- The expression of MHC-II and costimulators (CD80, CD86) sharply increases.
- The set of chemokine receptors changes: receptors for barrier tissues disappear and CCR7 and CXCR4 appear. These are what direct the cell to the T-zones of lymph nodes.
Upon reaching the T-zone, they turn into mature interdigitating cells (named so because T lymphocytes are densely packed between their "finger-like" processes).
Main subpopulations
The terminal differentiation products in humans are considered to be the DC1 and DC2 subpopulations, as well as specific tissue variants:
- Myeloid DCs (DC1): classical cells expressing the CD11c marker and the GM-CSF growth factor receptor (CD116). Upon maturation, they acquire the CD83 marker. Interacting with T lymphocytes, they promote their differentiation toward Th1 cells.
- Lymphoid DCs (DC2): lack CD11c, but feature high levels of the IL-3 receptor (CD123). Upon antigen presentation, they direct T lymphocyte differentiation along the Th2 pathway.
- Plasmacytoid DCs: circulate in the blood and contain many intracellular TLRs that recognize viral nucleic acids. In response to viral stimulation, they produce a colossal amount of type I interferons (IFN-alpha, beta, omega).
- Langerhans cells: an epidermal variety of myeloid origin. Their unique features are layered Birbeck granules in the cytoplasm, the langerin receptor (CD208), and the non-classical CD1a molecule required for the presentation of lipid antigens.
Briefly: answers to topical questions
Which pattern-recognition receptors (PRRs) are expressed by dendritic cells of different subpopulations?
Dendritic cells express various pattern-recognition receptors depending on the subpopulation and maturation stage.
- Myeloid dendritic cells — express TLR-1, 2, 3, 4, 5, 6, 8, 10. Immature cells additionally carry lectin receptors (mannose receptor, DEC-205, dectin-1, DC-SIGN), while mature cells retain the mannose receptor and DC-SIGN.
- Plasmacytoid dendritic cells — express TLR-1, 6, 7, 9, 10, as well as DEC-205 and dectin-1 lectin receptors.
In addition, scavenger receptors (SR-AI/II) are present on dendritic cells.
Which interleukins are secreted by myeloid dendritic cells (DC1) to induce a Th1 response?
To induce a Th1 response, myeloid dendritic cells, including DC1, secrete interleukin-12 (IL-12).
IL-12 is the main inducer of naive T helper cell differentiation into Th1 lymphocytes. Functional IL-12 is a heterodimer composed of p35 and p40 subunits; its producers include activated myeloid dendritic cells. The secretion of IL-12 by DC1 is associated with the development of a Th1 response.
What is the mechanism of processing and presentation of lipid antigens by the CD1a molecule in Langerhans cells?
Presentation of lipid antigens in Langerhans cells is carried out using the "non-classical" MHC-like molecule CD1a. The mechanism includes the following stages:
- Antigen incorporation — occurs in the endoplasmic reticulum with the participation of chaperones, similarly to the loading of MHC-I molecules. The cavity of the CD1 molecule has a high affinity for lipids.
- Recycling — CD1 molecules are endocytosed by the cell and follow an intracellular pathway similar to the formation of MHC-II-peptide complexes. This process is critical for the renewal of membrane molecules carrying the antigenic lipid.
Which transcription factors control the development of myeloid and plasmacytoid dendritic cells from progenitors?
The sources indicate transcription factors for the myeloid and lymphoid dendritic cell lineages.
| Cell type | Transcription factors |
|---|---|
| CD8− myeloid dendritic cells developing from a granulocyte-monocyte progenitor | Icaros, IRF-2, RelB, STAT3, PU1, Gfi1 |
| CD8− myeloid dendritic cells developing from a monocyte | Icaros, IRF-8, Id2, STAT3, PU1, Gfi1 |
| CD8+ lymphoid dendritic cells / pDC–LDC lineage | Icaros, IRF-8, Spi-B, PU1, Gfi1 |
For plasmacytoid dendritic cells, sources indicate their affiliation with the lymphoid lineage and the ability to differentiate into mature lymphoid dendritic cells, but a separate set of transcription factors specifically for plasmacytoid DCs is not provided.
DC1 are myeloid, stimulating a Th1 response (1 to 1). DC2 are lymphoid, stimulating a Th2 response (2 to 2).
Class and exam questions
What are tolerogenic dendritic cells?
These are semi-mature dendritic cells whose maturation took place under the influence of apoptotic cells or normal microflora (and the IL-10 cytokine). In lymph nodes, they selectively induce regulatory T cells, ensuring immune tolerance.
How do plasmacytoid dendritic cells enter the lymph node?
Unlike myeloid cells, which arrive via afferent lymph, plasmacytoid DCs enter the node directly from the bloodstream — through high endothelial venules, just like T lymphocytes do.
Can other cells perform dendritic cell functions?
Yes, during inflammation, endothelial and epithelial cells can express MHC-II and CD80/86 under the action of cytokines, acquiring limited antigen-presenting cell functions. After inflammation, this process is completely reversible.
What else to study on this topic
- Transcription factors of DC differentiation (Id2, IRF-8, PU1, etc.)
- Dendritic cell subpopulations in mice and the role of CD4/CD8 coreceptors
- Protocols for in vitro generation of myeloid DCs from monocytes
- Facultative immunocytes: the role of endothelium and epithelium in inflammation
- Mechanisms of lipid antigen presentation via CD1a in Langerhans cells
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