Unknown

Dataset Information

0

C-type lectin Mincle mediates cell death-triggered inflammation in acute kidney injury.


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 β-glucosylceramide as an endogenous Mincle ligand. Notably, free cholesterol markedly enhanced the agonistic effect of β-glucosylceramide on Mincle. Moreover, β-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 β-glucosylceramide in combination with free cholesterol acts on Mincle as an endogenous ligand to induce cell death-triggered, sustained inflammation after acute kidney injury.

SUBMITTER: Tanaka M 

PROVIDER: S-EPMC7596812 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC8819996 | biostudies-literature
| S-EPMC5347620 | biostudies-literature
| S-EPMC8363617 | biostudies-literature
2024-05-23 | GSE267242 | GEO
| S-EPMC2644135 | biostudies-literature
| S-EPMC3533529 | biostudies-literature
| S-EPMC7546328 | biostudies-literature
| S-EPMC9830509 | biostudies-literature
| S-EPMC4563757 | biostudies-literature
| S-EPMC7803412 | biostudies-literature