Mast Cells Signal their Importance in Health and Disease

Publication date: Available online 15 February 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Ana Olivera, Michael A. Beaven, Dean D. Metcalfe
FcεRI is the primary receptor in mast cells that mediate allergic reactions by inducing rapid release of mediators, an adaptive immune response that may have evolved as a host defense against parasites and venoms. Yet, it is apparent that mast cells are also activated via non-IgE receptors whose significance is just beginning to be understood. This includes the Mas-related GPCRs (MRGPRX2) that may contribute to reactions to diverse antimicrobials and polybasic compounds, and ADGRE2, an adhesion GPCR which is activated by mechanical vibration and whose variants are associated with familial vibratory urticaria. Mast cells similarly have long been recognized as the main repository for histamine, heparin and proteases. Recent evidence also points to new functions, modes of delivery and mechanisms of action of mast cell proteases that add new dimensions to the roles of mast cells in human biology. In addition, exposure of mast cells to environmental cues can quantitatively and qualitatively modulate their responses and thus their impact on allergic inflammation. Illustrating this paradigm, we summarize a number of recent studies implicating the injury/tissue damage cytokine IL-33 as a modulator of allergen-induced mast cell responses. We also discuss the discovery of markers associated with transformed mast cells and new potential directions in suppressing mast cell activity.



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