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  • Review Article
  • Published:

Transcriptional programming of the dendritic cell network

Nature Reviews Immunology volume 12, pages 101–113 (2012)Cite this article

Subjects

An Erratum to this article was published on 25 January 2013

Key Points

  • Dendritic cells (DCs) can be divided into multiple specialized subsets that are pivotal in bridging between the innate and adaptive immune responses.

  • Specification of DC subsets is initiated in the bone marrow and generates precursors committed to either the plasmacytoid DC (pDC) or conventional DC lineages.

  • Terminal differentiation occurs in both peripheral lymphoid organs and tissues in response to local environmental cues such as cytokines and inflammatory stimuli.

  • Transcription factors programme the specification and commitment of precursors to different DC subsets.

  • Shared transcription factor usage by DC subsets provides a common differentiation pathway for precursor cells, whereas terminal differentiation is often dictated by a single master regulator of that lineage (for example, E2-2 for pDCs and BATF3 for CD103+ DCs).

Abstract

Specialized subsets of dendritic cells (DCs) provide a crucial link between the innate and adaptive immune responses. The genetic programme that coordinates these distinct DC subsets is controlled by both cytokines and transcription factors. The initial steps in DC specification occur in the bone marrow and result in the generation of precursors committed to either the plasmacytoid or conventional DC pathways. DCs undergo further differentiation and lineage diversification in peripheral organs in response to local environmental cues. In this Review, we discuss new evidence regarding the coordination of the specification and commitment of precursor cells to different DC subsets and highlight the ensemble of transcription factors that control these processes.

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Figure 1: Differentiation and trafficking of DC subsets.
Figure 2: Growth factors and transcription factors that regulate DC differentiation.
Figure 3: Differential expression of transcription factors regulating DC differentiation.

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Acknowledgements

The authors thank R. Allan, A. Kallies, M. Chopin and M. Pellegrini for helpful discussions and critical reading of the manuscript. This work is supported by the National Health and Medical Research Council (NHMRC) of Australia and the Wellcome Trust. G.T.B. is supported by a Sylvia and Charles Viertel Foundation Fellowship and S.L.N. is supported by an Australian Research Council Future Fellowship. This work was made possible by Victorian State Government Operational Infrastructure Support and the Australian Government NHMRC Independent Research Institute Infrastructure Support Scheme.

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  1. Division of Molecular Immunology, Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Melbourne, 3052, Victoria, Australia

    Gabrielle T. Belz & Stephen L. Nutt

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Glossary

E protein

The E proteins (including E12, E47, HEB and E2-2) have emerged as key regulators of the immune system. They are a family of basic helix-loop-helix factors that work together with their antagonists, the ID proteins (ID1–ID4), to regulate lymphocyte development.

Lymphoid tissue-inducer cells

(LTi cells). A cell type that is present in developing lymph nodes, Peyer's patches and nasopharynx-associated lymphoid tissue (NALT). LTi cells are required for the development of these lymphoid organs. The inductive capacity of these cells for the generation of Peyer's patches and NALT has been shown by adoptive transfer, and it is generally assumed that they have a similar function in the formation of lymph nodes.

Nucleosome remodelling

Changes in the nucleosome structure are mediated by dedicated nuclear enzymes (for example, ATP-dependent nucleosome-remodelling enzymes) that change the accessibility of DNA and the expression of genes.

Histone modifications

Histones are essential to maintain DNA organization and may be modified by methylation and acetylation — changes that are thought to keep genes active or silent, respectively — thereby altering the genetic code read by transcriptional regulators.

NFAT

(Nuclear factor of activated T cells). A family of transcription factors that are regulated by calcium signalling and expressed by a variety of immune cells.

AP1

(Activator protein 1). A heterodimeric transcription factor that is composed of proteins belonging to the FOS, JUN and JUN-dimerization protein families. AP1 controls various cellular processes, including differentiation, proliferation and apoptosis.

Cross-priming

A mechanism by which immunogenic CD8+ T cells are activated by the presentation of an antigen that was not synthesized by the antigen-presenting cell itself.

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Belz, G., Nutt, S. Transcriptional programming of the dendritic cell network. Nat Rev Immunol 12, 101–113 (2012). https://doi.org/10.1038/nri3149

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