Extracts from the Lectures of the 32nd Nordic Congress of Dermato-Venereology, Tampere, Finland
Mast Cells in Dermatology
Plenary Lecture by Gunnar Nilsson:
Mast Cells and Skin
Mast cells and their mediators are often associated with different diseases, most commonly allergic diseases, but also skin
diseases like urticaria, angioedema, psoriasis atopic eczema or
skin tumours. However, mast cells are one of our evolutionary
oldest innate cells that have evolved to be equipped with an
arsenal of properties that can be used to protect us (1). They
have a favourable tissue distribution close to epithelial surface,
blood vessels and nerves, mast cells are endowed with a great
variety of receptors that the cells use to recognise and respond
to both endogenous and exogenous danger signals, including
pathogens (2). An interesting aspect of mast cell responses is
the broad effect mast cell mediators have on tissue responses,
including activation of sensory nerves, endothelial cells (causing vasodilation and extravasation), tissue remodelling, and
the recruitment and activation of other cells of the immune
system (3). In relation to this it is important to remember
that although mast cells have the capacity to release both
preformed mediators stored in the granules (e.g., histamine,
heparin, proteases), secrete lipid mediators (e.g., leukotrienes
and prostaglandins) and secrete de novo synthesised cytokines,
chemokines, interferons and growth factors, this does not
happen each time the mast cell is activated. The spectrum of
released mediators is dictated by the phenotype of the mast cell
and the trigger that induces mediator release. Some triggers like
IgE-receptor activation leads to degranulation, lipid mediators
as well as cytokine release. In contrast, CD30-activation only
induces release of chemokines and some pro-in?ammatory
cytokines (4). Thus, the view that mast cell-activation is rather
one-dimensional is not correct; instead one should look upon
mast cell activation as a multi-dimensional event with lots of
variation dependent on the situation. As a consequence, the
function of mast cells in different types of skin in?ammatory
diseases is rather complex (Fig. 1) (3, 5). In many cases mast
cell actions are pro-in?ammatory with the release of proteases
and TNF- , IL-8, interferon , etc; which are a driving force in
in?ammatory disorders like psoriasis and atopic eczema. In
contrast, under other circumstances mast cells can exhibit an
immuno-suppressive phenotype, with the release of IL-10 and
TGF- (Fig. 1). Ultraviolet radiation is one example of exposure
that can induce an immuno-suppressive mast cell phenotype
(6), which might play a role in epithelial skin cancers. To understand the multifaceted functions of mast cells in diverse
skin in?ammatory disorders is a big challenge, but nevertheless an important task to undertake. In the era of personalised
medicine and the design of new drugs for skin in?ammatory
diseases, it is of great importance to consider the many functions of mast cells in order to achieve an effective treatment.
References
1.
2.
3.
4.
5.
6.
Metz M, Maurer M. Mast cells – key effector cells in immune
responses. Trends Immunol 2007; 28: 234–241.
Abraham SN, St John AL. Mast cell-orchestrated immunity to
pathogens. Nat Rev Immunol 2010; 10: 440–452.
Harvima IT, Nilsson G. 2011. Mast cells as regulators of skin
in?ammation and immunity. Acta Derm Venereol 91: 644–650.
Fischer M, Harvima IT, Carvalho RFS, Möller C, Naukkarinen A,
Enblad G, Nilsson G. Mast cell CD30 ligand is up-regulated in
cutaneous in?ammation and mediates degranulation-independent
chemokine secretion. J Clin Invest 2006; 116: 2748–2756.
Harvima IT, Nilsson G, Suttle MM, Naukkarinen A. 2008. Is there
a role for mast cells in psoriasis? Arch Dermatol Res 300: 461–478.
Grimbaldeston MA, Nakae S, Kalesnikoff J, Tsai M, Galli SJ. Mast
cell-derived inter ????????????????????????????????????????????????????????????????????????????9??%?????(?????????????L????() U99H?9%1MM=8)
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