Genetic models of human and mouse dendritic cell development and function

Abstract

Dendritic cells (DCs) develop in the bone marrow from haematopoietic progenitors that have numerous shared characteristics between mice and humans. Human counterparts of mouse DC progenitors have been identified by their shared transcriptional signatures and developmental potential. New findings continue to revise models of DC ontogeny but it is well accepted that DCs can be divided into two main functional groups. Classical DCs include type 1 and type 2 subsets, which can detect different pathogens, produce specific cytokines and present antigens to polarize mainly naive CD8+ or CD4+ T cells, respectively. By contrast, the function of plasmacytoid DCs is largely innate and restricted to the detection of viral infections and the production of type I interferon. Here, we discuss genetic models of mouse DC development and function that have aided in correlating ontogeny with function, as well as how these findings can be translated to human DCs and their progenitors.

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Fig. 1: Genetic models of mouse dendritic cell development and lineage restriction.
Fig. 2: Stage-specific enhancer activation regulates Irf8-dependent specification of dendritic cell and monocyte progenitors.
Fig. 3: Specialized functions of mouse classical dendritic cell subsets.

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Glossary

Lineage tracing

A method to identify cells that are expressing or have expressed a gene of interest at any point during their development, which enables the study of progenitor–progeny relationships.

E protein

A member of a family of transcription factors, including TCF3 (also known as E2A), TCF4 (also known as E2-2) and TCF12 (also known as HEB), that are essential for the development of several haematopoietic lineages and that bind conserved DNA motifs known as E-boxes.

Checkpoint blockade

A type of immunotherapy that inhibits immune signalling cascades that are normally engaged to prevent autoimmunity and uncontrolled inflammation but that can also prevent effective immune responses to cancer, for example.

Type II immune responses

On recognition of parasites or activation by allergens, cytokines such as IL-4, IL-5, IL-13 and IL-10 are produced, and naive CD4+ T cells are polarized to T helper 2 cells.

Type III immune responses

On recognition of extracellular bacterial pathogens, cytokines such as IL-6, IL-17, IL-21, IL-22, IL-23 and transforming growth factor-β are produced, and naive T cells are polarized to T helper 17 cells.

Type I immune responses

On recognition of viral or intracellular bacterial pathogens, cytokines such as IL-2, IL-12 and interferon-γ are produced, and naive CD8+ and CD4+ T cells are polarized to cytotoxic T lymphocytes and T helper 1 cells, respectively.

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Anderson, D.A., Dutertre, C., Ginhoux, F. et al. Genetic models of human and mouse dendritic cell development and function. Nat Rev Immunol (2020). https://doi.org/10.1038/s41577-020-00413-x

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