Wednesday, July 15, 2026

5:45 PM - 6:30 PM

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Overview

Prof Francesca Levi-Schaffer

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Details

The pivotal effector cells of allergy are mast cells and eosinophils. Mast cells, as activated by IgE-dependent mechanisms via allergens, are the recognized starters while infiltrated and persistent eosinophils are the accepted damaging cells of the late stage and of the chronic outcome of allergy. Asthma and other allergic diseases’ management recently has benefited from the biological revolution, with an array of novel immunomodulatory therapeutic and investigational tools targeting different players of allergy at precise pathophysiological steps. Prominent examples include therapeutic monoclonal antibodies against cytokines, alarmins, and their receptors and small-molecule modifiers of signal transduction mainly mediated by Janus kinases and Bruton’s tyrosine kinases. However, and despite the new therapeutic options, meaningful improvements for allergic patients are not always achieved. For instance, approximately 30% of patients with severe asthma do not respond satisfactorily to classic medications nor to tailored biologics. Our aim has been to define better targeted anti-allergic drugs based on our in-depth knowledge of mast cells and of eosinophils. In the past we have defined a pro-inflammatory crosstalk between mast cells and eosinophils, the Allergic Effector Unit (AEU), that results in increased eosinophils chemotaxis, survival, degranulation, cytokine production and in enhanced mast cell survival, IgE-dependent and independent degranulation and cytokine production. We have identified the responsible released mediators (soluble interactions) and receptor/ligands couples (physical interactions) and proposed them as targets for therapy. Especially interesting are the activating "physical" AEU receptor/ligand CD48 expressed on both mast cells and eosinophils, and, at the same time, the inhibitory receptor CD300a that can indicate a possible anti-inflammatory or even pro-resolution activity of the cross-talking cells, within the AEU and in the allergic inflamed environment. Moreover, we have recently found that IgE-activated mast cells produce the specialized pro-resolving lipid mediators (SPMs) of the resolvin family. Therefore, as novel immunopharmacological interventions in allergic diseases we propose either to block CD48, that we have found to be related to severe asthma, or activate CD300a, important in the downregulation of atopic dermatitis, together with inducing a pro-resolution phenotype in the cells present in the allergic inflammatory environment. I will specifically discuss our most recent finding regarding CD300a function and its potential selective targeting on mast cells and their resolvin production and harnessing demonstrating for the first time that mast cells have the potential not only of initiating allergy but also stopping it. Translationally this strategy will have to consider the timing of the allergic reaction phases, its complexity and the allergic patient endotypes, to tailor a personalized therapy.

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