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Allergy is the host immune response towards harmless substances, called allergens. Allergic diseases comprise allergic asthma, allergic rhinitis, allergic conjunctivitis, atopic dermatitis, and food allergy. While some drugs counteract the symptoms and the inflammation arising from allergy, no completely effective and acceptable side effect free drug has been developed as yet. Moreover, severe asthma and atopic dermatitis are classified as unmet clinical needs. Mast cells and eosinophils are the main effector cells of the allergic response and thus, must be the first cells targeted to impede the allergic inflammation symptoms and evolution. The presence on mast cells and eosinophils of several surface receptors with either activating or inhibitory functions indicates the possibility of their pharmacological targeting. This review deals with some of the receptors expressed on mast cells and eosinophils and their ligand(s). Some receptors have already been exploited as drug targets and others can be feasibly utilized as novel targets for anti-allergic therapy. [ABSTRACT FROM AUTHOR]

Eosinophils are innate immune cells and active players in inflammatory responses. Their activation and increased levels in the blood and at specific sites are associated with parasitic infections and several inflammatory conditions, notably allergic diseases in which eosinophils are considered to be damaging cells. Intervention targeting eosinophils is thought to prevent and/or limit irreversible organ damage and other eosinophil-associated disorders like hypereosinophilic syndromes, some cancers and autoimmune diseases. Several eosinophil-targeted therapeutic agents which block specific steps in eosinophil differentiation, migration and activation have recently been developed, showing encouraging results and new insights into their specific role in allergy. Here, we review some potentially effective drug compounds, their drawbacks and future prospective focusing on allergic diseases. [ABSTRACT FROM AUTHOR]

Background We have recently observed that oxidative phosphorylation–mediated ATP production is essential for mast cell function. Pyruvate dehydrogenase (PDH) is the main regulator of the Krebs cycle and is located upstream of the electron transport chain. However, the role of PDH in mast cell function has not been described. Microphthalmia transcription factor (MITF) regulates the development, number, and function of mast cells. Localization of MITF to the mitochondria and its interaction with mitochondrial proteins has not been explored. Objective We sought to explore the role played by PDH in mast cell exocytosis and to determine whether MITF is localized in the mitochondria and involved in regulation of PDH activity. Methods Experiments were performed in vitro by using human and mouse mast cells, as well as rat basophil leukemia cells, and in vivo in mice. The effect of PDH inhibition on mast cell function was examined. PDH interaction with MITF was measured before and after immunologic activation. Furthermore, mitochondrial localization of MITF and its effect on PDH activity were determined. Results PDH is essential for immunologically mediated degranulation of mast cells. After activation, PDH is serine dephosphorylated. In addition, for the first time, we show that MITF is partially located in the mitochondria and interacts with PDH. This interaction is dependent on the phosphorylation state of PDH. Furthermore, mitochondrial MITF regulates PDH activity. Conclusion The association of mitochondrial MITF with PDH emerges as an important regulator of mast cell function. Our findings indicate that PDH could arise as a new target for the manipulation of allergic diseases. [ABSTRACT FROM AUTHOR]