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  • Review Article
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Human dendritic cell deficiency: the missing ID?

Nature Reviews Immunology volume 11, pages 575–583 (2011)Cite this article

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Key Points

  • Dendritic cells (DCs) are crucial for the induction of immune responses in mice, but whether they are similarly essential in humans remains largely untested owing to the lack of appropriate models.

  • Many human immunodeficiency states are known, but DC deficiency was only recently described. It is now appreciated that there are at least two forms of DC deficiency: due to mutation of GATA-binding factor 2 (GATA2) or mutation of interferon regulatory factor 8 (IRF8). Both lead to increased susceptibility to intracellular pathogens, notably mycobacteria.

  • GATA2 mutation causes DC, monocyte, B and NK lymphoid (DCML) deficiency, which is characterized by the loss of DCs, monocytes, B cells and NK cells. It has been described in about 30 patients worldwide, and these patients progress from immunodeficiency to global bone marrow failure.

  • IRF8 mutations have been reported in three patients. The recessive mutation K108E causes monocyte and DC deficiency with myeloproliferation, showing close similarities to IRF8-deficient mice.

  • The study of DC deficiency has further potential to illuminate the genetic factors and cellular pathways of DC differentiation in humans and to uncover the relationship between DCs and monocytes.

Abstract

Animal models and human in vitro systems indicate that dendritic cells (DCs) have a crucial role in priming naive T cells, but just how important are they in the intact human? Recent descriptions of human DC deficiency have begun to shed light on this question and to illuminate other puzzles of human DC biology, including their haematopoietic origin, developmental regulation and homeostatic equilibrium with other leukocytes. In this Review, we explore the recently described DC deficiency syndromes, discussing what these have taught us with regard to DC function in humans and the important issues that remain unsolved.

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Figure 1: DC classification in mice and humans.
Figure 2: Altered stem cell compartment in DC deficiency.

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Acknowledgements

The authors are supported by grants from the Medical Research Council, the Wellcome Trust, Leukaemia and Lymphoma Research, the Histiocytosis Association, the Histiocytosis Research Trust, the Newcastle Healthcare Charity and the Newcastle upon Tyne Hospitals NHS Charity. We thank F. Ginhoux for comments on the manuscript.

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  1. Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK

    Matthew Collin, Venetia Bigley, Muzlifah Haniffa & Sophie Hambleton

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Collin, M., Bigley, V., Haniffa, M. et al. Human dendritic cell deficiency: the missing ID?. Nat Rev Immunol 11, 575–583 (2011). https://doi.org/10.1038/nri3046

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