CD300c co-stimulates IgE-mediated basophils activation and its expression is increased in cow´s milk allergy

Publication date: Available online 12 June 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Olatz Zenarruzabeitia, Joana Vitallé, Iñigo Terrén, Ane Orrantia, Itziar Astigarraga, Leire Dopazo, Carlos Gonzalez, Laura Santos-Díez, Carlos Tutau, Pedro M. Gamboa, Agurtzane Bilbao, Francisco Borrego
BackgroundBasophils express high-affinity IgE receptors (FcεRI), which play an essential role in allergic diseases. To design promising immunomodulatory therapies, it is important to characterize new cell surface receptors that modulate immunoglobulin (Ig)E-mediated basophil activation threshold.ObjectivesTo analyze the expression of CD300 receptors on human basophils and their implication in IgE-mediated basophil activation processes.MethodsBlood samples from healthy and cow´s milk allergic patients were collected through the Basque Biobank under an institutional review board-approved protocol. Peripheral blood mononuclear cells (PBMCs) were obtained by density centrifugation, basophils were purified using a specific isolation kit, and phenotypical and functional studies were performed by flow cytometry.ResultsWe demonstrate that basophils express the activating receptor CD300c, which is specifically up-regulated in response to interleukin (IL)-3. CD300c works as a co-stimulatory molecule during IgE-mediated basophil activation, as shown by a significant increase in degranulation and cytokine production when basophils are activated in the presence of CD300c cross-linking compared with the activation through the IgE/FcεRI axis alone. Co-ligation of FcεRI and CD300c increased intracellular calcium mobilization and phosphorylation of signalling intermediates evoked only by FcεRI ligation. We show that the natural ligands of CD300c, phosphatidylserine and phosphatidylethanolamine, modulate IgE-mediated basophils activation. Furthermore, we have observed that the expression of CD300c in cow´s milk allergic children is increased compared to healthy controls, and that the intensity of expression correlates with the severity of the hypersensitivity symptoms.ConclusionCD300c could be considered as a biomarker and therapeutic target in IgE-mediated allergic diseases as it seems to be involved in the modulation of IgE-mediated basophils activation.



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