C-type lectin Mincle mediates cell death-triggered inflammation in acute kidney injury.
J Exp Med
; 217(11)2020 11 02.
Article
en En
| MEDLINE
| ID: mdl-32797195
ABSTRACT
Accumulating evidence indicates that cell death triggers sterile inflammation and that impaired clearance of dead cells causes nonresolving inflammation; however, the underlying mechanisms are still unclear. Here, we show that macrophage-inducible C-type lectin (Mincle) senses renal tubular cell death to induce sustained inflammation after acute kidney injury in mice. Mincle-deficient mice were protected against tissue damage and subsequent atrophy of the kidney after ischemia-reperfusion injury. Using lipophilic extract from the injured kidney, we identified ß-glucosylceramide as an endogenous Mincle ligand. Notably, free cholesterol markedly enhanced the agonistic effect of ß-glucosylceramide on Mincle. Moreover, ß-glucosylceramide and free cholesterol accumulated in dead renal tubules in proximity to Mincle-expressing macrophages, where Mincle was supposed to inhibit clearance of dead cells and increase proinflammatory cytokine production. This study demonstrates that ß-glucosylceramide in combination with free cholesterol acts on Mincle as an endogenous ligand to induce cell death-triggered, sustained inflammation after acute kidney injury.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Muerte Celular
/
Lectinas Tipo C
/
Lesión Renal Aguda
/
Proteínas de la Membrana
Límite:
Animals
Idioma:
En
Revista:
J Exp Med
Año:
2020
Tipo del documento:
Article
País de afiliación:
Japón