| First Author | Tanaka M | Year | 2020 |
| Journal | J Exp Med | Volume | 217 |
| Issue | 11 | PubMed ID | 32797195 |
| Mgi Jnum | J:298715 | Mgi Id | MGI:6477224 |
| Doi | 10.1084/jem.20192230 | Citation | Tanaka M, et al. (2020) C-type lectin Mincle mediates cell death-triggered inflammation in acute kidney injury. J Exp Med 217(11) |
| abstractText | 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 beta-glucosylceramide as an endogenous Mincle ligand. Notably, free cholesterol markedly enhanced the agonistic effect of beta-glucosylceramide on Mincle. Moreover, beta-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 beta-glucosylceramide in combination with free cholesterol acts on Mincle as an endogenous ligand to induce cell death-triggered, sustained inflammation after acute kidney injury. |
