The Journal of experimental medicine, 2020-11, Vol.217 (11)
2020
Details
- Autor(en) / Beteiligte
- Titel
- C-type lectin Mincle mediates cell death-triggered inflammation in acute kidney injury
- Ist Teil von
- The Journal of experimental medicine, 2020-11, Vol.217 (11)
- Ort / Verlag
- United States: Rockefeller University Press
- Erscheinungsjahr
- 2020
- Link zum Volltext
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0022-1007eISSN: 1540-9538DOI: 10.1084/jem.20192230Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7596812
- Format
- –
- Schlagworte
- Acute Kidney Injury - immunology, Acute Kidney Injury - metabolism, Animals, Cell Death - genetics, Cytokines - metabolism, Disease Models, Animal, Female, Glucosylceramidase - metabolism, Green Fluorescent Proteins - genetics, Inflammation - metabolism, Innate Immunity and Inflammation, Lectins, C-Type - deficiency, Lectins, C-Type - genetics, Lectins, C-Type - metabolism, Ligands, Macrophages - immunology, Macrophages - metabolism, Male, Membrane Proteins - deficiency, Membrane Proteins - genetics, Membrane Proteins - metabolism, Metabolism, Mice, Mice, Inbred C57BL, Mice, Knockout, Signal Transduction - genetics, Signal Transduction - immunology