Mast Cells in the Skin: Defenders of Integrity or Offenders in Inflammation?

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.

Automated summary

Mast cells are key effector cells in immediate-type allergic reactions, but they also play an important role in the first-line defense against pathogens, although this can lead to detrimental overshooting responses and exacerbation of inflammatory disorders. In the skin, mast cells have both beneficial functions in maintaining skin barrier integrity and host defense mechanisms, as well as causing inflammatory skin disorders, with their IgE-independent activation pathways playing a crucial role in sustained chronic skin inflammation and disease exacerbation.