Therapeutic normal IgG intravenous immunoglobulin activates Wnt-β-catenin pathway in dendritic cells.
Animals
Anti-Inflammatory Agents
/ pharmacology
Cells, Cultured
Dendritic Cells
/ drug effects
Encephalomyelitis, Autoimmune, Experimental
/ drug therapy
Female
Humans
Immunoglobulins, Intravenous
/ pharmacology
Mice
Mice, Inbred C57BL
T-Lymphocytes, Regulatory
/ drug effects
Th17 Cells
/ drug effects
Wnt Signaling Pathway
/ drug effects
beta Catenin
/ drug effects
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
04 03 2020
04 03 2020
Historique:
received:
10
10
2019
accepted:
12
02
2020
entrez:
6
3
2020
pubmed:
7
3
2020
medline:
22
6
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32132640
doi: 10.1038/s42003-020-0825-4
pii: 10.1038/s42003-020-0825-4
pmc: PMC7055225
doi:
Substances chimiques
Anti-Inflammatory Agents
0
Immunoglobulins, Intravenous
0
beta Catenin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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