Dectin-1 Binding to Annexins on Apoptotic Cells Induces Peripheral Immune Tolerance via NADPH Oxidase-2.
Aging
/ metabolism
Animals
Annexins
/ chemistry
Antigens
/ metabolism
Apoptosis
Autoimmunity
Binding Sites
Conserved Sequence
/ genetics
Drosophila
Female
Humans
Immunosuppression Therapy
Jurkat Cells
Lectins, C-Type
/ metabolism
Male
Mice, Knockout
NADPH Oxidase 2
/ metabolism
NF-kappa B
/ metabolism
Peripheral Tolerance
Phosphorylation
Protein Binding
Protein Domains
Reactive Oxygen Species
/ metabolism
Syk Kinase
/ metabolism
beta-Glucans
/ metabolism
Dectin-1
NOX-2
SYK
annexin (A1, A5, and A13)
apoptotic cells
autoimmunity
biased agonism
dendritic cells
peripheral immune tolerance
reactive oxygen species
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
24 12 2019
24 12 2019
Historique:
received:
19
03
2019
revised:
18
07
2019
accepted:
20
11
2019
entrez:
26
12
2019
pubmed:
26
12
2019
medline:
29
9
2020
Statut:
ppublish
Résumé
Uptake of apoptotic cells (ACs) by dendritic cells (DCs) and induction of a tolerogenic DC phenotype is an important mechanism for establishing peripheral tolerance to self-antigens. The receptors involved and underlying signaling pathways are not fully understood. Here, we identify Dectin-1 as a crucial tolerogenic receptor binding with nanomolar affinity to the core domain of several annexins (annexin A1, A5, and A13) exposed on ACs. Annexins bind to Dectin-1 on a site distinct from the interaction site of pathogen-derived β-glucans. Subsequent tolerogenic signaling induces selective phosphorylation of spleen tyrosine kinase (SYK), causing activation of NADPH oxidase-2 and moderate production of reactive oxygen species. Thus, mice deficient for Dectin-1 develop autoimmune pathologies (autoantibodies and splenomegaly) and generate stronger immune responses (cytotoxic T cells) against ACs. Our data describe an important immunological checkpoint system and provide a link between immunosuppressive signals of ACs and maintenance of peripheral immune tolerance.
Identifiants
pubmed: 31875551
pii: S2211-1247(19)31577-3
doi: 10.1016/j.celrep.2019.11.086
pii:
doi:
Substances chimiques
Annexins
0
Antigens
0
Lectins, C-Type
0
NF-kappa B
0
Reactive Oxygen Species
0
beta-Glucans
0
dectin 1
0
NADPH Oxidase 2
EC 1.6.3.-
Syk Kinase
EC 2.7.10.2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4435-4446.e9Informations de copyright
Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.