| Autor: |
Kevin Bode, Fatmire Bujupi, Corinna Link, Tobias Hein, Stephanie Zimmermann, Diluka Peiris, Vincent Jaquet, Bernd Lepenies, Heiko Weyd, Peter H. Krammer |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
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| Zdroj: |
Cell Reports, Vol 29, Iss 13, Pp 4435-4446.e9 (2019) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2019.11.086 |
| Popis: |
Summary: 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. : Bode et al. identify Dectin-1 on dendritic cells as a receptor for apoptotic-cell-bound annexins responsible for the induction of peripheral immune tolerance. Tolerogenic signaling depends on selective SYK phosphorylation and the production of reactive oxygen species via NADPH oxidase-2. Dectin-1-deficient mice generate stronger immune responses against apoptotic cells and develop autoimmunity. Keywords: Dectin-1, annexin (A1, A5, and A13), apoptotic cells, dendritic cells, peripheral immune tolerance, autoimmunity, SYK, NOX-2, reactive oxygen species, biased agonism |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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