CD300c costimulates IgE-mediated basophil activation, and its expression is increased in patients with cow's milk allergy
| Autor: | Leire Dopazo, Joana Vitallé, Pedro M. Gamboa, Laura Santos-Díez, Itziar Astigarraga, Iñigo Terrén, Olatz Zenarruzabeitia, Carlos Tutau, Carlos Rodríguez González, Francisco Borrego, Agurtzane Bilbao, Ane Orrantia |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Allergy Thymic stromal lymphopoietin Adolescent Immunology chemical and pharmacologic phenomena Milk allergy Immunoglobulin E Peripheral blood mononuclear cell 03 medical and health sciences 0302 clinical medicine parasitic diseases medicine Immunology and Allergy Animals Humans Receptor Child Cells Cultured Membrane Glycoproteins biology business.industry Degranulation Infant hemic and immune systems Receptor Cross-Talk Allergens medicine.disease Milk Proteins Basophils Up-Regulation Basophil activation 030104 developmental biology Child Preschool Antigens Surface biology.protein Cattle Female Milk Hypersensitivity business Biomarkers 030215 immunology Signal Transduction |
| Zdroj: | The Journal of allergy and clinical immunology. 143(2) |
| ISSN: | 1097-6825 |
| Popis: | Background Basophils express high-affinity IgE receptors (FceRI), which play an essential role in allergic diseases. It is important to characterize new cell-surface receptors that modulate IgE-mediated basophil activation threshold to design promising immunomodulatory therapies. Objectives We sought to analyze the expression of CD300 receptors on human basophils and their implication in IgE-mediated basophil activation processes. Methods Blood samples from healthy subjects and patients with cow's milk allergy were collected through the Basque Biobank under an institutional review board–approved protocol. PBMCs were obtained by means of density centrifugation, basophils were purified with a specific isolation kit, and phenotypic and functional studies were performed by using flow cytometry. Results We demonstrate that basophils express the activating receptor CD300c, which is specifically upregulated in response to IL-3. CD300c works as a costimulatory 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 activation through the IgE/FceRI axis alone. Coligation of FceRI and CD300c increased intracellular calcium mobilization and phosphorylation of signaling intermediates evoked only by FceRI ligation. We show that the natural ligands of CD300c, phosphatidylserine and phosphatidylethanolamine, modulate IgE-mediated basophil activation. Furthermore, we have observed that CD300c expression in children with cow's milk allergy is increased compared with that in healthy control subjects and that the intensity of expression correlates with the severity of the hypersensitivity symptoms. Conclusion CD300c could be considered a biomarker and therapeutic target in patients with IgE-mediated allergic diseases because it seems to be involved in the modulation of IgE-mediated basophil activation. |
| Databáze: | OpenAIRE |
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