2026-06-14T06:44:09Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/65022025-06-13T10:50:14Zcom_20.500.12105_19604com_20.500.12105_2051com_20.500.12105_15322com_20.500.12105_2052col_20.500.12105_19605col_20.500.12105_16961col_20.500.12105_19617
Repisalud
author
del Fresno, Carlos
author
Sanz-Leal, Paula
author
Enamorado, Michel
author
Wculek, Stefanie K
author
Martinez-Cano, Sarai
author
Blanco-Menendez, Noelia
author
Schulz, Oliver
author
Gallizioli, Mattia
author
Miró-Mur, Francesc
author
Cano, Eva
author
Planas, Anna
author
Sancho, David
funder
Asociación Española Contra el Cáncer
funder
Ministerio de Ciencia, Innovación y Universidades (España)
funder
European Molecular Biology Organization
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Comunidad de Madrid (España)
funder
Instituto de Salud Carlos III
funder
Fundación La Marató TV3
funder
Unión Europea. Comisión Europea
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
funder
Fundación ProCNIC
2018-10-22T13:18:00Z
2018-10-22T13:18:00Z
2018-10-19
Science. 2018; 362(6412):351-356
10.1126/science.aan8423
1095-9203
0036-8075
Science
30337411
http://hdl.handle.net/20.500.12105/6502
Host injury triggers feedback mechanisms that limit tissue damage. Conventional type 1 dendritic cells (cDC1s) express dendritic cell natural killer lectin group receptor-1 (DNGR-1), encoded by the gene Clec9a, which senses tissue damage and favors cross-presentation of dead-cell material to CD8+ T cells. Here we find that DNGR-1 additionally reduces host-damaging inflammatory responses induced by sterile and infectious tissue injury in mice. DNGR-1 deficiency leads to exacerbated caerulein-induced necrotizing pancreatitis and increased pathology during systemic Candida albicans infection without affecting fungal burden. This effect is B and T cell-independent and attributable to increased neutrophilia in DNGR-1-deficient settings. Mechanistically, DNGR-1 engagement activates SHP-1 and inhibits MIP-2 (encoded by Cxcl2) production by cDC1s during Candida infection. This consequently restrains neutrophil recruitment and promotes disease tolerance. Thus, DNGR-1-mediated sensing of injury by cDC1s serves as a rheostat for the control of tissue damage, innate immunity, and immunopathology.
eng
DNGR-1 in dendritic cells limits tissue damage by dampening neutrophil recruitment
research article
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DNGR-1inDCSLimitsTissue_2018_SUPPL.pdf.txt
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