Type I allergies are pathological, type 2 inflammatory immune responses against otherwise harmless environmental allergens that arise from complex interactions between different types of immune cells. Activated immune cells undergo extensive changes in phenotype and function to fulfill their effector functions. Hereby, activation, differentiation, proliferation, migration, and mounting of effector responses require metabolic reprogramming. While the metabolic changes associated with activation of dendritic cells, macrophages, and T cells are extensively studied, data about the metabolic phenotypes of the other cell types critically involved in allergic responses (epithelial cells, eosinophils, basophils, mast cells, and ILC2s) are rather limited. This review briefly covers the basics of cellular energy metabolism and its connection to immune cell function. In addition, it summarizes the current state of knowledge in terms of dendritic cell and macrophage metabolism and subsequently focuses on the metabolic changes associated with activation of epithelial cells, eosinophils, basophils, mast cells, as well as ILC2s in allergy. Interestingly, the innate key cell types in allergic inflammation were reported to change their metabolic phenotype during activation, shifting to either glycolysis (epithelial cells, M1 macrophages, DCs, eosinophils, basophils, acutely activated mast cells), oxidative phosphorylation (M2 macrophages, longer term activated mast cells), or fatty acid oxidation (ILC2s). Therefore, immune metabolism is of relevance in allergic diseases and its connection to immune cell effector function needs to be considered to better understand induction and maintenance
| INTRODUC TI ONAllergic diseases are an increasing health and economic problem in developed countries with IgE-mediated type I hypersensitivity disorders reported to affect more than 25% of the population. 1,2 Immunologically, onset and maintenance of type I allergies are caused by exaggerated type 2-mediated immune responses, directed against otherwise harmless environmental antigens. The main effector cells involved in establishment and elicitation of allergic reactions are antigen-presenting cells (dendritic cells (DCs) and macrophages), Th2 cells, IgE-producing plasma cells, eosinophils, basophils, mast cells, and innate-like lymphocytes type II cells (ILC2s).Additionally, lipid mediators derived from arachidonic acid such as prostaglandins (PGs, eg, PGD4, PGE2) and leukotrienes (LTs, eg, cysLT1), or the peptide hormone histamine (derived from histidine) are produced by activated immune cells within minutes, act locally through specific receptors expressed on many target cells, and are usually quickly metabolized. 3,4 These molecules are prominently involved in the hallmark features of allergic inflammation by inducing potent and bronchoconstriction/long-lasting bronchospasm, immune cell recruitment, airway inflammation, hyperresponsiveness, and remodeling. [3][4][5] Activated immune cells can undergo extensive phenotypic changes in order ...