Dermal dendritic cell

As a link between innate and acquired (adaptive) immunity, dendriticcells, as professional antigen-presenting cells, occupy a prominent position in the immune system.

Dermal dendritic cells (DDC), belonging to the myeloid dendritic cells, are preferentially localized around the dermal vascular plexus. They are characterized by a lobulated nucleus as well as an irregularly configured cytoplasm.

Dendritic branches characteristic of epidermal dendritic cells, Langerhans cells, are absent in this dendritic subspecies. Also absent are the Birbeck granules typical of Langerhans cells. The essential task of the DDCs is the stimulation of naive T cells.

Dermal (myeloid) dendritic cells, in contrast to plasmacytoid dendritic cells, express CD11c and CD33 and larger amounts of MHC II, but not CD123. The most characteristic marker for DDCs is the marker CD1c (BDCA1). In contrast, CD1a, which is strongly expressed on Langerhans cells, is only weakly represented.

Dermal (myeloid) dendritic cells are potent producers of TNF-alpha and interleukin-12 or interleukin-23 depending on the type of antigenic stimulation (Hoene V et al. 2006).

It was originally assumed that myeloid dendritic cells induce preferentially Th1-oriented immune responses and that, in contrast, plasmacytoid dendritic cells induce preferentially Th2-oriented immune responses (Hoene V et al. 2006). DDCs are equipped with a large spectrum of PPRs (Pattern Recognition Receptors). This plays an essential role for transdermal defence functions of pathogens (allergens, microbial pathogens) (Lee CH et al. 2015; Hirai KE et al. 2016). Activated DDCs migrate into the regional lymph nodes where they induce the specific antigen response against the absorbed antigens.

The TLR (toll-like receptor) spectrum of myeloid dendritic cells includes a broad expression of toll-like receptors: TLR-1,-2, -3, -4, -5, -6, -7, -8 and TLR-10, as well as lectins and the mannose receptor (CD206).

DDCs can produce either IL-12 or IL-23 depending on the type and structure of the inducing stimulus. Either type 1 or type 17 accentuated T cell responses are induced.

Pigmentary incontinence and DDCs: It has been suggested that the dermal melanin that occurs in lichenoid inflammatory dermatoses is absorbed exclusively by macophages(melanophages). In fact, melanin uptake is also by dermal dendritic cells. These answer this uptake with an increased expression of the chemokines MIP-1beta(CCL4) and MCP-1(CCL2) (Müller M et al.2013).

1. Hoene V et al (2006) Human monocyte-derived dendritic cells express TLR9 and react directly to the CpG-A oligonucleotides D19 J Leukoc Biol 80:1328-1336.
2. Hirai KE et al (2016) Langerhans cells (CD1a and CD207), dermal dendrocytes (FXIIIa) and plasmacytoid dendritic cells (CD123) in skin lesions of leprosy patients. Microb pathog 91:18-25.
3. Lee CH et al (2015) Dermal dendritic cells, but not Langerhans cells, are critical in murine single epicutaneous sensitization. Exp Dermatol 24:67-69.
4. Bacci S et al (2014) Immunohistochemical analysis of dendritic cells in skin lesions: correlations with survival time. Forensic Sci Int 244:179-185.
5. Flacher V et al (2014) Murine Langerin+ dermal dendritic cells prime CD8+ T cells while Langerhans cells induce cross-tolerance. EMBO Mol Med 6:1191-1204.
6. Müller M et al (2013) Alterations in the secretory pattern of dermal dendritic cells following melanin uptake. Cell Tissue Res 352:599 610.
7. Rothenfusser S et al. (2002) Plasmacytoid dendritic cells: the key to CpG. Hum Immunol 63:1111-1119.