CD300c costimulates IgE-mediated basophil activation, and its expression is increased in patients with cow's milk allergy - 07/02/19
, Joana Vitallé, MSc a, Iñigo Terrén, MSc a, Ane Orrantia, MSc a, Itziar Astigarraga, MD, PhD b, c, d, Leire Dopazo, MD a, c, Carlos Gonzalez, MD, PhD d, e, Laura Santos-Díez, MD a, c, Carlos Tutau, MD, PhD c, Pedro M. Gamboa, MD, PhD a, f, Agurtzane Bilbao, MD a, c, Francisco Borrego, MD, PhD a, g, h, ⁎ Abstract |
Background |
Basophils express high-affinity IgE receptors (FcεRI), 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/FcεRI axis alone. Coligation of FcεRI and CD300c increased intracellular calcium mobilization and phosphorylation of signaling intermediates evoked only by FcεRI 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.
Le texte complet de cet article est disponible en PDF.Key words : Basophils, CD300, CD300a, CD300c, allergy, IgE-mediated activation, IL-3, activation threshold
Abbreviations used : APC, cIMDM, Erk, fMLP, FMO, ITAM, ITIM, JAK, PC, PE, PerCP, PS, STAT, TSLP
Plan
| Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest. |
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| Supported by a grant from “Instituto de Salud Carlos III” through the project PI16/01223 (cofunded by European Regional Development Fund “A way to make Europe”). J.V. is a recipient of a predoctoral contract funded by the Department of Education, Language Policy and Culture, Basque Government (PRE_2017_2_0242). I.T. is recipient of a fellowship from the Jesús de Gangoiti Barrera Foundation (FJGB17/003). O.Z. is recipient of a postdoctoral contract funded by “Instituto de Salud Carlos III-Contratos Sara Borrell 2017 (CD17/00128)” and the European Social Fund (ESF)-The ESF invests in your future. F.B. is an Ikerbasque Research Professor, Ikerbaque, Basque Foundation for Science. |
Vol 143 - N° 2
P. 700 - février 2019 Retour au numéro
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