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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...

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Autores principales: 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
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
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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.
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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
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