期刊
FRONTIERS IN IMMUNOLOGY
卷 10, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2019.03146
关键词
C-type lectin receptor; dendritic cells; immunity; inflammation; DNGR-1; Clec9a; cross-presentation
类别
资金
- PhD La Caixa fellowship [LCF/BQ/ES14/10320011]
- AECC Foundation [INVES192DELF]
- CNIC
- European Research Council [725091]
- European Commission [635122]
- Ministerio de Ciencia, Innovacion e Universidades (MICINN)
- Agencia Estatal de Investigacion and Fondo Europeo de Desarrollo Regional (FEDER) [SAF2016-79040-R]
- Comunidad de Madrid [B2017/BMD-3733]
- FIS-Instituto de Salud Carlos III
- MICINN
- FEDER [RD16/0015/0018-REEM]
- Acteria Foundation
- Atresmedia (Constantes y Vitales prize)
- Fundacio La Marato de TV3 [201723]
- Instituto de Salud Carlos III (ISCIII)
- Pro CNIC Foundation
- Severo Ochoa Center of Excellence [SEV-2015-0505]
- European Research Council (ERC) [725091] Funding Source: European Research Council (ERC)
DNGR-1 (encoded by CLEC9A) is a C-type lectin receptor (CLR) with an expression profile that is mainly restricted to type 1 conventional dendritic cells (cDC1s) both in mice and humans. This delimited expression pattern makes it appropriate for defining a cDC1 signature and for therapeutic targeting of this population, promoting immunity in mouse models. Functionally, DNGR-1 binds F-actin, which is confined within the intracellular space in healthy cells, but is exposed when plasma membrane integrity is compromised, as happens in necrosis. Upon F-actin binding, DNGR-1 signals through SYK and mediates cross-presentation of dead cell-associated antigens. Cross-presentation to CD8(+) T cells promoted by DNGR-1 during viral infections is key for cross-priming tissue-resident memory precursors in the lymph node. However, in contrast to other closely related CLRs such as Dectin-1, DNGR-1 does not activate NF kappa B. Instead, recent findings show that DNGR-1 can activate SHP-1 to limit inflammation triggered by heterologous receptors, which results in reduced production of inflammatory chemokines and neutrophil recruitment into damaged tissues in both sterile and infectious processes. Hence, DNGR-1 reduces immunopathology associated with tissue damage, promoting disease tolerance to safeguard tissue integrity. How DNGR-1 signals are conditioned by the microenvironment and the detailed molecular mechanisms underlying DNGR-1 function have not been elucidated. Here, we review the expression pattern and structural features of DNGR-1, and the biological relevance of the detection of tissue damage through this CLR.
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