Intravenous immunoglobulin induces IL-4 in human basophils by signaling through surface-bound IgE.

Autor: Galeotti C; Institut National de la Santé et de la Recherche Médicale and Centre de Recherche des Cordeliers, Equipe-Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, Paris, France; Service de Rhumatologie Pédiatrique, Centre de Référence des Maladies Auto-Inflammatoires rares et des Amyloses, CHU de Bicêtre, Le Kremlin Bicêtre, France., Stephen-Victor E; Institut National de la Santé et de la Recherche Médicale and Centre de Recherche des Cordeliers, Equipe-Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, Paris, France., Karnam A; Institut National de la Santé et de la Recherche Médicale and Centre de Recherche des Cordeliers, Equipe-Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, Paris, France., Das M; Institut National de la Santé et de la Recherche Médicale and Centre de Recherche des Cordeliers, Equipe-Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, Paris, France., Gilardin L; Institut National de la Santé et de la Recherche Médicale and Centre de Recherche des Cordeliers, Equipe-Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, Paris, France; Département de Médecine Interne et Immunologie Clinique, Hôpital Pitié-Salpêtrière, AP-HP, Paris, France., Maddur MS; Institut National de la Santé et de la Recherche Médicale and Centre de Recherche des Cordeliers, Equipe-Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France., Wymann S; Research Department, CSL Behring AG, Bern, Switzerland., Vonarburg C; Research Department, CSL Behring AG, Bern, Switzerland., Chevailler A; Laboratoire d'Immunologie et d'Allergologie, CHU d'Angers, Université d'Angers, INSERM Unité 1232, LabEx IGO 'Immuno-Graft-Onco', Angers, France., Dimitrov JD; Institut National de la Santé et de la Recherche Médicale and Centre de Recherche des Cordeliers, Equipe-Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France., Benveniste O; Département de Médecine Interne et Immunologie Clinique, Hôpital Pitié-Salpêtrière, AP-HP, Paris, France; Sorbonne Université, Institut National de la Santé et de la Recherche Médicale Unité 974, Paris, France., Bruhns P; Institut Pasteur, Department of Immunology, Unit of Antibodies in Therapy and Pathology, Paris, France; INSERM, U1222, Paris, France., Kaveri SV; Institut National de la Santé et de la Recherche Médicale and Centre de Recherche des Cordeliers, Equipe-Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France., Bayry J; Institut National de la Santé et de la Recherche Médicale and Centre de Recherche des Cordeliers, Equipe-Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France. Electronic address: jagadeesh.bayry@crc.jussieu.fr.
Jazyk: angličtina
Zdroj: The Journal of allergy and clinical immunology [J Allergy Clin Immunol] 2019 Aug; Vol. 144 (2), pp. 524-535.e8. Date of Electronic Publication: 2018 Dec 07.
DOI: 10.1016/j.jaci.2018.10.064
Abstrakt: Background: Therapeutic normal IgG or intravenous immunoglobulin (IVIG) exerts anti-inflammatory effects through several mutually nonexclusive mechanisms. Recent data in mouse models of autoimmune disease suggest that IVIG induces IL-4 in basophils by enhancing IL-33 in SIGN-related 1-positive innate cells. However, translational insight on these data is lacking.
Objective: We sought to investigate the effect of IVIG on human basophil functions.
Methods: Isolated circulating basophils from healthy donors were cultured in the presence of IL-3, IL-33, GM-CSF, thymic stromal lymphopoietin, or IL-25. The effect of IVIG and F(ab') 2 and Fc IVIG fragments was examined based on expression of various surface molecules, phosphorylation of spleen tyrosine kinase, induction of cytokines, and histamine release. Basophil phenotypes were also analyzed from IVIG-treated patients with myopathy. Approaches, such as depletion of anti-IgE reactivity from IVIG, blocking antibodies, or inhibitors, were used to investigate the mechanisms.
Results: We report that IVIG directly induces activation of IL-3-primed human basophils, but IL-33 and other cytokines were dispensable for this effect. Activation of basophils by IVIG led to enhanced expression of CD69 and secretion of IL-4, IL-6, and IL-8. IVIG-treated patients with myopathy displayed enhanced expression of CD69 on basophils. The spleen tyrosine kinase pathway is implicated in these functions of IVIG and were mediated by F(ab') 2 fragments. Mechanistically, IVIG induced IL-4 in human basophils by interacting with basophil surface-bound IgE but independent of FcγRII, type II Fc receptors, C-type lectin receptors, and sialic acid-binding immunoglobulin-like lectins.
Conclusion: These results uncovered a pathway of promoting the T H 2 response by IVIG through direct interaction of IgG with human basophils.
(Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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