Publication date: Available online 7 December 2018
Source: Journal of Allergy and Clinical Immunology
Author(s): Caroline Galeotti, Emmanuel Stephen-Victor, Anupama Karnam, Mrinmoy Das, Laurent Gilardin, Mohan S. Maddur, Sandra Wymann, Cédric Vonarburg, Alain Chevailler, Jordan D. Dimitrov, Olivier Benveniste, Pierre Bruhns, Srini V. Kaveri, Jagadeesh Bayry
Abstract
Background
Therapeutic normal immunoglobulin G or intravenous immunoglobulin (IVIG) exerts anti-inflammatory effects via several mutually nonexclusive mechanisms. Recent data in mouse models of autoimmune diseases suggest that IVIG induces IL-4 in basophils by enhancing IL-33 in SIGN-R1+ 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 the healthy donors were cultured in the presence of IL-3, IL-33, GM-CSF, TSLP or IL-25. The effect of IVIG, F(ab')2 and Fc fragments of IVIG was examined on the expression of various surface molecules, phosphorylation of Syk, induction of cytokines, and histamine release. Phenotype of basophils was also analyzed from IVIG-treated myopathy patients. 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. The activation of basophils by IVIG led to enhanced expression of CD69 and secretion of IL-4, IL-6 and IL-8. IVIG-treated myopathy patients displayed enhanced expression of CD69 on the basophils. Syk pathway is implicated in these functions of IVIG and were mediated via 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 Siglecs.
Conclusion
These results uncovered a pathway of promoting Th2 response by IVIG through direct interaction of IgG with human basophils.
Graphical abstract
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