NOD1 deficiency promotes inflammation via autophagic degradation of ASK1
Abstract Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) is a pattern recognition receptor of bacterial peptidoglycans. NOD1 facilitates the elimination of invading intracellular bacteria via autophagy induction. Here, we demonstrate that NOD1 exerts an anti-inflammatory effect...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-05-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-08213-6 |
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| _version_ | 1850127928095932416 |
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| author | Yoshitaka Kimura Miyako Kimura Noriko Miura Yusuke Yoshino Hajime Kono |
| author_facet | Yoshitaka Kimura Miyako Kimura Noriko Miura Yusuke Yoshino Hajime Kono |
| author_sort | Yoshitaka Kimura |
| collection | DOAJ |
| description | Abstract Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) is a pattern recognition receptor of bacterial peptidoglycans. NOD1 facilitates the elimination of invading intracellular bacteria via autophagy induction. Here, we demonstrate that NOD1 exerts an anti-inflammatory effect mediated via the selective autophagy of host cell protein. In our study of Candida albicans water-soluble fraction (CAWS)-induced coronary arteritis, which is a mouse model of Kawasaki disease, we observed an exacerbated disease phenotype in NOD1-deficient mice. NOD1 deficiency induced a higher expression of inflammatory cytokines via CAWS and CAWS-induced endoplasmic reticulum (ER) stress in bone marrow-derived dendritic cells. Furthermore, exaggerated inflammation was dependent on apoptosis signal-regulated kinase 1 (ASK1). Notably, NOD1 directly interacted with ASK1, inducing selective autophagy of ASK1, which was dependent on ATG16L1, and thus competitively inhibiting ER stress-dependent ASK1 activation. Altogether, these results show that NOD1 modulates excessive inflammatory responses through the upregulation of autophagy. |
| format | Article |
| id | doaj-art-e527c6633c05459ea430abb78fe3c159 |
| institution | OA Journals |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-e527c6633c05459ea430abb78fe3c1592025-08-20T02:33:32ZengNature PortfolioCommunications Biology2399-36422025-05-018111410.1038/s42003-025-08213-6NOD1 deficiency promotes inflammation via autophagic degradation of ASK1Yoshitaka Kimura0Miyako Kimura1Noriko Miura2Yusuke Yoshino3Hajime Kono4Department of Microbiology and Immunology, Teikyo University School of MedicineDepartment of Internal Medicine, Teikyo University School of MedicineCenter for the Advancement of Pharmaceutical Education, Tokyo University of Pharmacy and Life SciencesDepartment of Microbiology and Immunology, Teikyo University School of MedicineDepartment of Internal Medicine, Teikyo University School of MedicineAbstract Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) is a pattern recognition receptor of bacterial peptidoglycans. NOD1 facilitates the elimination of invading intracellular bacteria via autophagy induction. Here, we demonstrate that NOD1 exerts an anti-inflammatory effect mediated via the selective autophagy of host cell protein. In our study of Candida albicans water-soluble fraction (CAWS)-induced coronary arteritis, which is a mouse model of Kawasaki disease, we observed an exacerbated disease phenotype in NOD1-deficient mice. NOD1 deficiency induced a higher expression of inflammatory cytokines via CAWS and CAWS-induced endoplasmic reticulum (ER) stress in bone marrow-derived dendritic cells. Furthermore, exaggerated inflammation was dependent on apoptosis signal-regulated kinase 1 (ASK1). Notably, NOD1 directly interacted with ASK1, inducing selective autophagy of ASK1, which was dependent on ATG16L1, and thus competitively inhibiting ER stress-dependent ASK1 activation. Altogether, these results show that NOD1 modulates excessive inflammatory responses through the upregulation of autophagy.https://doi.org/10.1038/s42003-025-08213-6 |
| spellingShingle | Yoshitaka Kimura Miyako Kimura Noriko Miura Yusuke Yoshino Hajime Kono NOD1 deficiency promotes inflammation via autophagic degradation of ASK1 Communications Biology |
| title | NOD1 deficiency promotes inflammation via autophagic degradation of ASK1 |
| title_full | NOD1 deficiency promotes inflammation via autophagic degradation of ASK1 |
| title_fullStr | NOD1 deficiency promotes inflammation via autophagic degradation of ASK1 |
| title_full_unstemmed | NOD1 deficiency promotes inflammation via autophagic degradation of ASK1 |
| title_short | NOD1 deficiency promotes inflammation via autophagic degradation of ASK1 |
| title_sort | nod1 deficiency promotes inflammation via autophagic degradation of ask1 |
| url | https://doi.org/10.1038/s42003-025-08213-6 |
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