2. Academic Validation
  3. NOD1 deficiency promotes inflammation via autophagic degradation of ASK1

NOD1 deficiency promotes inflammation via autophagic degradation of ASK1

  • Commun Biol. 2025 May 21;8(1):781. doi: 10.1038/s42003-025-08213-6.
Yoshitaka Kimura 1 2,  Miyako Kimura 3 4,  Noriko Miura 5,  Yusuke Yoshino 6 7,  Hajime Kono 3
Affiliations

Affiliations

  • 1 Department of Microbiology and Immunology, Teikyo University School of Medicine, Tokyo, Japan. yo.kimura.july@med.teikyo-u.ac.jp.
  • 2 Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan. yo.kimura.july@med.teikyo-u.ac.jp.
  • 3 Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.
  • 4 Division of Regenerative Therapy, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
  • 5 Center for the Advancement of Pharmaceutical Education, Tokyo University of Pharmacy and Life Sciences, Hachioji, Japan.
  • 6 Department of Microbiology and Immunology, Teikyo University School of Medicine, Tokyo, Japan.
  • 7 Asia International Institute of Infectious Disease Control, Teikyo University, Tokyo, Japan.
PMID: 40399666 DOI: 10.1038/s42003-025-08213-6
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.

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