Modulation of Mast Cell Reactivity by Lipids: The Neglected Side of Allergic Diseases

Abstract

Mast cells (MCs) have long been mainly regarded as effector cells in IgE-associated allergic disorders with potential immunoregulatory roles. Located close to the allergen entry sites in the skin and mucosa, MCs can capture foreign substances such as allergens, toxins, or noxious substances and are exposed to the danger signals produced by epithelial cells. MC reactivity shaped by tissue-specific factors is crucial for allergic responses ranging from local skin reactions to anaphylactic shock. Development of Th2 response leading to allergen-specific IgE production is a prerequisite for MC sensitization and induction of FcεRI-mediated MC degranulation. Up to now, IgE production has been mainly associated with proteins, whereas lipids present in plant pollen grains, mite fecal particles, insect venoms, or food have been largely overlooked regarding their immunostimulatory and immunomodulatory properties. Recent studies, however, have now demonstrated that lipids affect the sensitization process by modulating innate immune responses of epithelial cells, dendritic cells, and NK-T cells and thus crucially contribute to the outcome of sensitization. Whether and how lipids affect also MC effector functions in allergic reactions has not yet been fully clarified. Here, we discuss how lipids can affect MC responses in the context of allergic inflammation. Direct effects of immunomodulatory lipids on MC degranulation, changes in local lipid composition induced by allergens themselves and changes in lipid transport affecting MC reactivity are possible mechanisms by which the function of MC might be modulated.

Keywords: allergy; degranulation; flippases; floppases; lipid mediators; lipids; mast cells; scramblases.

Figure 1

Modulation of MC reactivity by allergen-associated lipids and lipid mediators.

Figure 2

Potential effects of flippases, floppases, and scramblases on MC function. Lipid transporting enzymes could be involved in regulation of different cellular processes. Granule biogenesis (A), endocytosis (B), and exocytosis (C) could be regulated by flippases. Floppases are participating in transport of lipid mediators (D) and could be involved in regulation of MC exocytosis (E). Scramblases regulate FcεRI-mediated signaling and MC degranulation (F), could be potentially involved in TLR-signaling in endosomes (G) and regulation of gene transcription (H).