Contributors: Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)); École Pratique des Hautes Études (EPHE); Université Paris Sciences et Lettres (PSL)-Université Paris Sciences et Lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU); Immunopathologie et immunointervention thérapeutique (CRC - Inserm U1138); Université Paris Sciences et Lettres (PSL)-Université Paris Sciences et Lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-École Pratique des Hautes Études (EPHE); Hôpital Bicêtre AP-HP, Le Kremlin-Bicêtre; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP); CHU Pitié-Salpêtrière AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU); Université Sorbonne Paris Cité (USPC); CLS Behring AG, Bern; Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7); Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA); Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE); Université de Nantes (UN)-Université de Nantes (UN)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE); Université de Nantes (UN)-Université de Nantes (UN); LabEX IGO Immunothérapie Grand Ouest; Nantes Université (Nantes Univ); Centre Hospitalier Universitaire d'Angers (CHU Angers); PRES Université Nantes Angers Le Mans (UNAM); Centre de recherche en Myologie – U974 SU-INSERM; Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU); Anticorps en thérapie et pathologie - Antibodies in Therapy and Pathology; Institut Pasteur Paris (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM); Supported by Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie, Université Paris Descartes and CSL Behring, Switzerland. CG is a recipient of fellowship from La Fondation pour la Recherche Médicale (FDM20150633674), France; ESV and AK are recipient of fellowships from Indo-French Center for Promotion of Advanced Research (CEFIPRA).; ANR-11-LABX-0016,IGO,Immunothérapies Grand Ouest(2011)
نبذة مختصرة : International audience ; 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 TH2 response by IVIG through direct interaction of IgG with human basophils.
Processing Request
No Comments.