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  • Review Article
  • Published:

Role of mast cells in allergic and non-allergic immune responses: comparison of human and murine data

Nature Reviews Immunology volume 7, pages 93–104 (2007)Cite this article

Key Points

  • Our view of human mast cells has broadened. In the past, they were established as crucial effector cells of allergic inflammation; now, they are increasingly recognized as cells that regulate many tissue functions, such as blood flow and coagulation, smooth-muscle contraction and peristalsis of the intestine, mucosal secretion, wound healing and regulation of innate and adaptive immune responses, including tolerance.

  • Laboratory tools to study human mast cells are limited; therefore, many mast-cell studies have been carried out using murine mast cells. This has not always been clearly indicated in review articles or in the titles of original articles.

  • There are important functional differences between human and murine mast cells, such as receptor expression (for example, Fcγ receptors and functional TLRs), responsiveness to cytokines (for example, IL-3 and IL-4) and mediator expression (for example, proteases, IL-4, IL-5 and TNF). These differences limit extrapolation from murine data to the human situation.

  • Human mast cells seem to be more closely related to monocytes and macrophages, whereas human basophils share properties mainly with eosinophils.

  • Mast-cell inhibitors, such as ligands of ITIM-containing receptors (FcγRIIb and CD300a), the anti-inflammatory cytokines IL-10 and TGFβ1, CD200 and intracellular signalling molecules that modulate FcεRI-mediated mast-cell activation, are a new and exciting area of mast-cell research that is just starting to be unravelled for human mast cells.

  • The role of mast cells in allergic inflammation is complex and is not restricted to the immediate phase of IgE-mediated reactions. Mast-cell mediators affect the mucosa, the blood vessels and sensory nerves at sites of allergy; mast-cell proteases and cytokines contribute to the initiation of a facultative late-phase reaction by recruiting and activating eosinophils, neutrophils and TH2 cells; and mast-cell-derived signals (such as IL-13 and CD40L) might contribute to IgE synthesis.

Abstract

The versatile role of mast cells in allergy, in innate immune responses and in the regulation of tissue homeostasis is well recognized. However, it is often not made clear that most mast-cell data derive solely from experiments in mice or rats, species that obviously never suffer from allergic and most other mast-cell-associated human diseases. Data on human mast cells are limited, and the mast-cell source and species from which findings derive are frequently not indicated in the titles and summaries of research publications. This Review summarizes recent data on human mast cells, discusses differences with murine mast cells, and describes new tools to study this increasingly meaningful cell type in humans.

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Figure 1: Proposed functions of human mast cells under normal conditions.
Figure 2: Comparison between human mast cells and related bone-marrow-derived cells.
Figure 3: Inhibitory signals for mast-cell mediator release induced by FcεRI aggregation.
Figure 4: Role of mast cells in allergic inflammation.

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Acknowledgements

I thank all previous and current fellows in my former laboratory in Hannover (1992–2004) and my current laboratory in Stuttgart (since 2005) for their engagement in mast-cell research. In particular, I thank C. Dahinden and J. Bienenstock for continuous discussions.

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  1. Department of Nutritional Medicine & Immunology, University of Hohenheim, Fruwirthstr. 12, Stuttgart, D-70593, Germany

    Stephan C. Bischoff

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Glossary

'Wheal and flare' reaction

The acute response of the skin to allergen in a skin-prick test. The wheal refers to the swelling, the flare refers to the reddening of the skin over a wider area that is induced by vasodilation, local oedema and neuronal mechanisms.

Type I hypersensitivity

Immunological hypersensitivity reactions have been classified by Coombs and Gell into four types depending on the antigen-recognizing molecule. Type I hypersensitivity is defined as an IgE-mediated hypersensitivity reaction, also known as an 'anaphylaxis reaction', consisting of an early phase (wheal and flare reaction) and a facultative late-phase reaction.

Type III hypersensitivity

An immune-complex-mediated hypersensitivity reaction; the immune complexes consist of exogenous or endogenous antigens and IgG.

Immunoreceptor tyrosine-based inhibitory motif

(ITIM). A structural motif containing tyrosine residues that is found in the cytoplasmic tails of several inhibitory receptors, such as FcγRIIb. The prototype six-amino-acid ITIM sequence is (Ile/Val/Leu/Ser)-Xaa-Tyr-Xaa-Xaa-(Leu/Val). Ligand-induced clustering of these inhibitory receptors results in tyrosine phosphorylation, often by SRC-family tyrosine kinases, which provides a docking site for the recruitment of cytoplasmic phosphatases that have an SH2 domain.

Late-phase reaction

IgE-mediated allergic reactions occurring within a few minutes (early-phase reaction) can be followed by a facultative secondary response phase starting typically 2–4 hours after allergen challenge. This late-phase anaphylaxis, in contrast to the early phase, is characterized by a pronounced cellular infiltration at the site of allergen challenge, which might lead to long-lasting inflammation and tissue dysfunction.

Type IV hypersensitivity

T-cell-mediated hypersensitivity reactions, also known as delayed-type hypersensitivity reactions. Despite some similarities to the late-phase reactions in the course of type I hypersensitivity reactions, they are separated because they are not preceded by an IgE-dependent early-phase reaction.

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Bischoff, S. Role of mast cells in allergic and non-allergic immune responses: comparison of human and murine data. Nat Rev Immunol 7, 93–104 (2007). https://doi.org/10.1038/nri2018

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