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Therapeutic normal IgG intravenous immunoglobulin activates Wnt-β-catenin pathway in dendritic cells

Abstract : Therapeutic normal IgG intravenous immunoglobulin (IVIG) is a well-established first-line immunotherapy for many autoimmune and inflammatory diseases. Though several mechanisms have been proposed for the anti-inflammatory actions of IVIG, associated signaling pathways are not well studied. As β-catenin, the central component of the canonical Wnt pathway, plays an important role in imparting tolerogenic properties to dendritic cells (DCs) and in reducing inflammation, we explored whether IVIG induces the β-catenin pathway to exert anti-inflammatory effects. We show that IVIG in an IgG-sialylation independent manner activates β-catenin in human DCs along with upregulation of Wnt5a secretion. Mechanistically, β-catenin activation by IVIG requires intact IgG and LRP5/6 co-receptors, but FcγRIIA and Syk are not implicated. Despite induction of β-catenin, this pathway is dispensable for anti-inflammatory actions of IVIG in vitro and for mediating the protection against experimental autoimmune encephalomyelitis in vivo in mice, and reciprocal regulation of effector Th17/Th1 and regulatory T cells.
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Submitted on : Friday, April 24, 2020 - 2:26:24 PM
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Anupama Karnam, Naresh Rambabu, Mrinmoy Das, Melissa Bou-Jaoudeh, Sandrine Delignat, et al.. Therapeutic normal IgG intravenous immunoglobulin activates Wnt-β-catenin pathway in dendritic cells. Communications Biology, Nature Publishing Group, 2020, 3 (1), pp.96. ⟨10.1038/s42003-020-0825-4⟩. ⟨inserm-02553449⟩

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