Dendritic Cells


Dendritic cells (DCs) are distributed in almost all tissues body, acting as sentinels of the immune system. They serve as specialised pathogen‐sensing and antigen‐presenting cells that initiate and regulate the immune response. DCs are derived from unique progenitors present in the bone marrow, which seed the tissues where they differentiate into mature DCs. Transcriptomic, phenotypic and functional analyses indicate that human and murine DCs can be divided into three subsets: two subsets of conventional DCs (cDC) named cDC1 and cDC2, and a third lineage of plasmacytoid DCs (pDCs). Each subset is unique and has distinct functional specialisations to control specific T‐cell responses. DCs form a complex cellular network capable of integrating multiple environmental signals and can induce either immunity or tolerance. As a consequence, DCs are suitable candidates for therapeutic intervention in immune‐mediated conditions.

Key Concepts

  • Dendritic cells are a heterogeneous group of specialised pathogen‐sensing and antigen‐presenting cells.
  • They are distributed in almost all tissues and organs, and act as sentinels of the immune system.
  • They are derived from DC‐restricted progenitors present in the bone marrow and arise from a dedicated lineage.
  • They can be grouped into three subsets based on ontogeny and transcription factor dependency: two lineages of conventional DCs named cDC1 and cDC2, as well as a third lineage of plasmacytoid DCs (pDCs).
  • Each subset is unique and has distinct functional specialisations.
  • The cDC1 subset is efficient at cross‐presentation, and elicits Th1 responses.
  • The cDC2 subset is capable of eliciting Th2 and Th17 responses.
  • pDCs produce large amounts of type I interferons to combat viral infections.

Keywords: dendritic cell; conventional dendritic cell; plasmacytoid DC; pDC; development; ontogeny; immune function; immune response; dendritic cell subsets; cDC1; cDC2

Figure 1. Dendritic cells control adaptive immunity. Dendritic cells constantly sample the environment for antigens. They phagocytose exogenous antigens, process and present them on either MHC class I or MHC class II molecules. Upon activation, they migrate to the draining lymph node where they present the processed antigens to either naïve CD8+ or CD4+ T cells. cDC1 is shown to be better than cDC2 at cross‐presentation of antigens to naïve CD8+ T cells and CD4+ T cells via MHC class I and II molecules, respectively. Hence, generating cytotoxic T lymphocytes and inducing Th1 immunity, which are important in the clearance of intracellular viruses and bacteria. On the other hand, cDC2 is better than cDC1 in presentation of processed antigens to naïve CD4+ T cells via MHC class II molecules. This results in the induction of Th2 or Th17 immunity, which is important in the clearance of extracellular pathogens, parasites and allergens. pDCs secrete type I interferons to combat viral infections.
Figure 2. Development of DC subsets. DC development begins in the bone marrow. Haematopoietic stem cells differentiate into monocyte‐macrophage dendritic cell progenitors (MDPs), which have both monocyte and dendritic cells potential. MDPs differentiate into the common dendritic cell progenitors (CDPs), which are committed to the DC lineage and common monocyte progenitor (cMOP) that differentiate into monocytes. Within the CDPs, a proportion of cells are committed towards the pDC lineage, while others differentiate into pre‐DCs, which are committed towards the cDC lineage. Mature pDCs exit the bone marrow and enter the circulation to seed the lymphoid tissues. In mouse, pre‐committed pre‐DCs enter the circulation to seed both lymphoid and non‐lymphoid tissues and differentiate into cDC1 or cDC2 subsets. Whether pre‐committed pre‐DCs exist in humans is still unknown. In humans, circulating pre‐DCs are found in the blood but it is unclear if they are precursors of circulating blood dendritic cells or whether they seed the tissues directly or indirectly via circulating pre‐committed pre‐DCs or blood dendritic cells.


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Further Reading

Merad M, Ginhoux F and Collin M (2008) Origin, homeostasis and function of Langerhans cells and other langerin‐expressing dendritic cells. Nature Reviews Immunology 8: 935–947.

Mildner A and Jung S (2014) Development and function of dendritic cell subsets. Immunity 40: 642–656.

Mildner A, Yona S and Jung S (2013) A close encounter of the third kind: monocyte‐derived cells. Advances in Immunology 120: 69–103.

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See, Peter, and Ginhoux, Florent(Dec 2015) Dendritic Cells. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0001125.pub4]