Abstract
Mast cells (MCs) are best-known as key effector cells of immediate-type allergic reactions that may even culminate in life-threatening anaphylactic shock syndromes. However, strategically positioned at the host–environment interfaces and equipped with a plethora of receptors, MCs also play an important role in the first-line defense against pathogens. Their main characteristic, the huge amount of preformed proinflammatory mediators embedded in secretory granules, allows for a rapid response and initiation of further immune effector cell recruitment. The same mechanism, however, may account for detrimental overshooting responses. MCs are not only detrimental in MC-driven diseases but also responsible for disease exacerbation in other inflammatory disorders. Focusing on the skin as the largest immune organ, we herein review both beneficial and detrimental functions of skin MCs, from skin barrier integrity via host defense mechanisms to MC-driven inflammatory skin disorders. Moreover, we emphasize the importance of IgE-independent pathways of MC activation and their role in sustained chronic skin inflammation and disease exacerbation.
Highlights
The skin is one of the body’s largest organs and serves as a barrier to the outer environment [1,2]
Mast cells (MCs) play a significant role in the production of IL-12, which is needed for the protection of the host from polymicrobial infections [155]
In the case of C. albicans, a fungus that can infect the skin but can cause systemic infections, a recent study has shown that recognition of the fungi by rat bone marrow-derived MCs (BMMCs) through the C lectin type receptor (CLR) Dectin 1 led to MC degranulation and release of tumor necrosis factor (TNF)-α, IL-6, IL-10, CCL2, CCL4 and NOS [192]
Summary
The skin is one of the body’s largest organs and serves as a barrier to the outer environment [1,2]. MCs continuously secrete tumor necrosis factor (TNF) [36], IL-1β [41,42], IL-4 [43,44,45,46,47], bFGF/FGF-2 [48,49,50], transforming growth factor β1 (TGF-β1) [51] and VEGF/VPF [52,53] These mediators have recently been reported to influence FB functions [6,34,36,54,55], but the direct MC–FB interaction via these cytokines remains to be proven. The homeostatic environment of the skin is regulated very precisely, and MCs play a crucial role in maintaining skin barrier homeostasis and integrity by interacting with neighboring non-immune cells, like FBs, KCs and ECs [58]
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