Dectin-1 Binding to Annexins on Apoptotic Cells Induces Peripheral Immune Tolerance via NADPH Oxidase-2.
Cell Rep
; 29(13): 4435-4446.e9, 2019 12 24.
Article
em En
| MEDLINE
| ID: mdl-31875551
ABSTRACT
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 ß-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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Apoptose
/
Anexinas
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Lectinas Tipo C
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Tolerância Periférica
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NADPH Oxidase 2
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article