NK-cell–elicited gasdermin-D–dependent hepatocyte pyroptosis induces neutrophil extracellular traps that facilitate HBV-related acute-on-chronic liver failure
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Le résumé fourni par la source
BACKGROUND AND AIMS: HBV infection is a major etiology of acute-on-chronic liver failure (ACLF). At present, the pattern and regulation of hepatocyte death during HBV-ACLF progression are still undefined. Evaluating the mode of cell death and its inducers will provide new insights for developing therapeutic strategies targeting cell death. In this study, we aimed to elucidate whether and how immune landscapes trigger hepatocyte death and lead to the progression of HBV-related ACLF. APPROACH AND RESULTS: We identified that pyroptosis represented the main cell death pattern in the liver of patients with HBV-related ACLF. Deficiency of MHC-I in HBV-reactivated hepatocytes activated cytotoxic NK cells, which in turn operated in a perforin/granzyme-dependent manner to trigger GSDMD/caspase-8-dependent pyroptosis of hepatocytes. Neutrophils selectively accumulated in the pyroptotic liver, and HMGB1 derived from the pyroptotic liver constituted an important factor triggering the generation of pathogenic extracellular traps in neutrophils (NETs). Clinically, elevated plasma levels of myeloperoxidase-DNA complexes were a promising prognostic biomarker for HBV-related ACLF. More importantly, targeting GSDMD pyroptosis-HMGB1 release in the liver abrogates NETs that intercept the development of HBV-related ACLF. CONCLUSIONS: Studying the mechanisms that selectively modulate GSDMD-dependent pyroptosis, as well as its immune landscapes, will provide a novel strategy for restoring the liver function of patients with HBV-related ACLF.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- NK-cell–elicited gasdermin-D–dependent hepatocyte pyroptosis induces neutrophil extracellular traps that facilitate HBV-related acute-on-chronic liver failure
- Date Crossref
- 27/03/2024
- Éditeur
- Ovid Technologies (Wolters Kluwer Health)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Sun Yat-sen University The First Affiliated Hospital pays non établi dans la noticeUniversité ou école supérieure
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Key Laboratory of Guangdong Province pays non établi dans la noticeStructure de recherche
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Third Affiliated Hospital of Sun Yat-sen University pays non établi dans la noticeÉtablissement de santé
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Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation) pays non établi dans la noticeOrganisation à but non lucratif
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Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology pays non établi dans la noticeStructure de recherche
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School of Life Sciences Guangdong Province Key Laboratory of Pharmaceutical Functional Genes pays non établi dans la noticeUniversité ou école supérieure
The First Affiliated Hospital — Sun Yat-sen University, Key Laboratory of Guangdong Province et Third Affiliated Hospital of Sun Yat-sen University, avec 3 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.