Therapeutic normal IgG intravenous immunoglobulin activates Wnt-?-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 ?-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 ?-catenin pathway to exert anti-inflammatory effects. We show that IVIG in an IgG-sialylation independent manner activates ?-catenin in human DCs along with upregulation of Wnt5a secretion. Mechanistically, ?-catenin activation by IVIG requires intact IgG and LRP5/6 co-receptors, but Fc?RIIA and Syk are not implicated. Despite induction of ?-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.

SUBMITTER: Karnam A 

PROVIDER: S-EPMC7055225 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature