Mast cells signal their importance in health and disease

Abstract

FcεRI is the primary receptor in mast cells that mediates allergic reactions by inducing rapid release of mediators, an adaptive immune response that might have evolved as a host defense against parasites and venoms. Yet it is apparent that mast cells are also activated through non-IgE receptors, the significance of which is just beginning to be understood. This includes the Mas-related G protein-coupled receptor X2, which might contribute to reactions to diverse antimicrobials and polybasic compounds, and the adhesion G protein-coupled receptor E2, variants of which are associated with familial vibratory urticaria and are activated by mechanical vibration. Similarly, mast cells 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 effect 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.

Killer Immunoglobulin-Like Receptor 2DL4 (CD158d) Regulates Human Mast Cells both Positively and Negatively: Possible Roles in Pregnancy and Cancer Metastasis

“…As mentioned above, interference with the KIT-mediated and FcεRI-mediated signal pathways has been proposed as a potential strategy to control mast cell-mediated allergic reactions [13,14], highlighting the importance of KIR2DL4 as a target for allergic diseases. In other words, the agonistic antibodies against KIR2DL4 would be useful for allergy therapy, similar to the anti-IgE antibody omalizumab clinically utilized to neutralize IgE in blood, and eliminate of FcεRI-mediated function and control mast cell-mediated allergic reactions [56].…”

Mast cells—Good guys with a bad image?

“…[60][61][62] However, in case of chronic urticarial, the α-chain of the FcεRI receptor is attacked by autoantibodies. 66,67 FcεRI-mediated responses are also regulated by the presence of specific ligands such as prostaglandin E2, SCF, Toll-like receptor ligands, IL-33, as well as ligands of G protein-coupled receptors such as adenosine, macrophage inflammatory protein 1α, and RANTES that stimulate responses to antigen resulting in an augmented degranulation or cytokine production. 22,64,65 Degranulation of MCs leads to the secretion of vasoactive and inflammatory mediators that are the reason for symptoms.…”

“…Current knowledge is that other non IgE-receptors, such as G protein-coupled receptors or ligand-gated ion channels, can be involved in the reaction. 66,67 FcεRI-mediated responses are also regulated by the presence of specific ligands such as prostaglandin E2, SCF, Toll-like receptor ligands, IL-33, as well as ligands of G protein-coupled receptors such as adenosine, macrophage inflammatory protein 1α, and RANTES that stimulate responses to antigen resulting in an augmented degranulation or cytokine production. 32 Allergic reactions to different allergens are associated with the activation of specific MCs subsets, for example, in mice CTMCs contribute to systemic anaphylaxis, whereas both CTMCs and MMCs are involved in allergic reactions to food.…”

The Role of Mast Cells in IgE-Independent Lung Diseases

“…As described above, human MCs are heterogeneous and are often characterized by the neutral protease content within granules, e.g., MCTC skin mast cells and MCT lung mast cells [28]. MC granule subpopulations can be further defined at the ultrastructural and protein content level.…”