Cargando…
C-type lectin Mincle mediates cell death–triggered inflammation in acute kidney injury
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 dea...
Autores principales: | , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596812/ https://www.ncbi.nlm.nih.gov/pubmed/32797195 http://dx.doi.org/10.1084/jem.20192230 |
_version_ | 1783602191452340224 |
---|---|
author | Tanaka, Miyako Saka-Tanaka, Marie Ochi, Kozue Fujieda, Kumiko Sugiura, Yuki Miyamoto, Tomofumi Kohda, Hiro Ito, Ayaka Miyazawa, Taiki Matsumoto, Akira Aoe, Seiichiro Miyamoto, Yoshihiro Tsuboi, Naotake Maruyama, Shoichi Suematsu, Makoto Yamasaki, Sho Ogawa, Yoshihiro Suganami, Takayoshi |
author_facet | Tanaka, Miyako Saka-Tanaka, Marie Ochi, Kozue Fujieda, Kumiko Sugiura, Yuki Miyamoto, Tomofumi Kohda, Hiro Ito, Ayaka Miyazawa, Taiki Matsumoto, Akira Aoe, Seiichiro Miyamoto, Yoshihiro Tsuboi, Naotake Maruyama, Shoichi Suematsu, Makoto Yamasaki, Sho Ogawa, Yoshihiro Suganami, Takayoshi |
author_sort | Tanaka, Miyako |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7596812 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-75968122021-05-02 C-type lectin Mincle mediates cell death–triggered inflammation in acute kidney injury Tanaka, Miyako Saka-Tanaka, Marie Ochi, Kozue Fujieda, Kumiko Sugiura, Yuki Miyamoto, Tomofumi Kohda, Hiro Ito, Ayaka Miyazawa, Taiki Matsumoto, Akira Aoe, Seiichiro Miyamoto, Yoshihiro Tsuboi, Naotake Maruyama, Shoichi Suematsu, Makoto Yamasaki, Sho Ogawa, Yoshihiro Suganami, Takayoshi J Exp Med Article 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. Rockefeller University Press 2020-08-14 /pmc/articles/PMC7596812/ /pubmed/32797195 http://dx.doi.org/10.1084/jem.20192230 Text en This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Article Tanaka, Miyako Saka-Tanaka, Marie Ochi, Kozue Fujieda, Kumiko Sugiura, Yuki Miyamoto, Tomofumi Kohda, Hiro Ito, Ayaka Miyazawa, Taiki Matsumoto, Akira Aoe, Seiichiro Miyamoto, Yoshihiro Tsuboi, Naotake Maruyama, Shoichi Suematsu, Makoto Yamasaki, Sho Ogawa, Yoshihiro Suganami, Takayoshi C-type lectin Mincle mediates cell death–triggered inflammation in acute kidney injury |
title | C-type lectin Mincle mediates cell death–triggered inflammation in acute kidney injury |
title_full | C-type lectin Mincle mediates cell death–triggered inflammation in acute kidney injury |
title_fullStr | C-type lectin Mincle mediates cell death–triggered inflammation in acute kidney injury |
title_full_unstemmed | C-type lectin Mincle mediates cell death–triggered inflammation in acute kidney injury |
title_short | C-type lectin Mincle mediates cell death–triggered inflammation in acute kidney injury |
title_sort | c-type lectin mincle mediates cell death–triggered inflammation in acute kidney injury |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596812/ https://www.ncbi.nlm.nih.gov/pubmed/32797195 http://dx.doi.org/10.1084/jem.20192230 |
work_keys_str_mv | AT tanakamiyako ctypelectinminclemediatescelldeathtriggeredinflammationinacutekidneyinjury AT sakatanakamarie ctypelectinminclemediatescelldeathtriggeredinflammationinacutekidneyinjury AT ochikozue ctypelectinminclemediatescelldeathtriggeredinflammationinacutekidneyinjury AT fujiedakumiko ctypelectinminclemediatescelldeathtriggeredinflammationinacutekidneyinjury AT sugiurayuki ctypelectinminclemediatescelldeathtriggeredinflammationinacutekidneyinjury AT miyamototomofumi ctypelectinminclemediatescelldeathtriggeredinflammationinacutekidneyinjury AT kohdahiro ctypelectinminclemediatescelldeathtriggeredinflammationinacutekidneyinjury AT itoayaka ctypelectinminclemediatescelldeathtriggeredinflammationinacutekidneyinjury AT miyazawataiki ctypelectinminclemediatescelldeathtriggeredinflammationinacutekidneyinjury AT matsumotoakira ctypelectinminclemediatescelldeathtriggeredinflammationinacutekidneyinjury AT aoeseiichiro ctypelectinminclemediatescelldeathtriggeredinflammationinacutekidneyinjury AT miyamotoyoshihiro ctypelectinminclemediatescelldeathtriggeredinflammationinacutekidneyinjury AT tsuboinaotake ctypelectinminclemediatescelldeathtriggeredinflammationinacutekidneyinjury AT maruyamashoichi ctypelectinminclemediatescelldeathtriggeredinflammationinacutekidneyinjury AT suematsumakoto ctypelectinminclemediatescelldeathtriggeredinflammationinacutekidneyinjury AT yamasakisho ctypelectinminclemediatescelldeathtriggeredinflammationinacutekidneyinjury AT ogawayoshihiro ctypelectinminclemediatescelldeathtriggeredinflammationinacutekidneyinjury AT suganamitakayoshi ctypelectinminclemediatescelldeathtriggeredinflammationinacutekidneyinjury |