PUBLICATION

Tissue-resident trained immunity in hepatocytes protects against septic liver injury in zebrafish

Authors
Wang, Z., Liu, Y., Hu, J., You, X., Yang, J., Zhang, Y., Liu, Q., Yang, D.
ID
ZDB-PUB-240609-10
Date
2024
Source
Cell Reports   43: 114324114324 (Journal)
Registered Authors
Yang, Dahai
Keywords
CP: Immunology, H3K4me3, hepatocytes, mitophagy, pyroptosis, septic-liver injury, trained immunity, zebrafish, β-glucan
MeSH Terms
  • Immunity, Innate
  • Sepsis*/immunology
  • Liver/immunology
  • Liver/metabolism
  • Liver/pathology
  • Hepatocytes*/immunology
  • Hepatocytes*/metabolism
  • Pyroptosis*
  • Lipopolysaccharides
  • Zebrafish Proteins*/genetics
  • Zebrafish Proteins*/metabolism
  • Histones/metabolism
  • Lectins, C-Type/metabolism
  • Zebrafish*
  • Animals
  • Mitophagy
  • beta-Glucans/pharmacology
  • Trained Immunity
(all 18)
PubMed
38850536 Full text @ Cell Rep.
Abstract
Trained immunity is classically characterized by long-term functional reprogramming of innate immune cells to combat infectious diseases. Infection-induced organ injury is a common clinical severity phenotype of sepsis. However, whether the induction of trained immunity plays a role in protecting septic organ injury remains largely unknown. Here, through establishing an in vivo β-glucan training and lipopolysaccharide (LPS) challenge model in zebrafish larvae, we observe that induction of trained immunity could inhibit pyroptosis of hepatocytes to alleviate septic liver injury, with an elevated trimethyl-histone H3 lysine 4 (H3K4me3) modification that targets mitophagy-related genes. Moreover, we identify a C-type lectin domain receptor in zebrafish, named DrDectin-1, which is revealed as the orchestrator in gating H3K4me3 rewiring-mediated mitophagy activation and alleviating pyroptosis-engaged septic liver injury in vivo. Taken together, our results uncover tissue-resident trained immunity in maintaining liver homeostasis at the whole-animal level and offer an in vivo model to efficiently integrate trained immunity for immunotherapies.
Genes / Markers
Figures
Figure Gallery (6 images)
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Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
gz15aTgTransgenic Insertion
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    Human Disease / Model
    No data available
    Sequence Targeting Reagents
    Target Reagent Reagent Type
    cldc1CRISPR1-cldc1CRISPR
    cldc1CRISPR2-cldc1CRISPR
    cldc1CRISPR3-cldc1CRISPR
    cldc1CRISPR4-cldc1CRISPR
    gsdmebCRISPR2-gsdmebCRISPR
    1 - 5 of 5
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    Fish
    Fish
    AB
    AB + CRISPR1-cldc1 + CRISPR2-cldc1 + CRISPR3-cldc1 + CRISPR4-cldc1
    gz15aTg/gz15aTg
    1 - 3 of 3
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    Antibodies
    Orthology
    No data available
    Engineered Foreign Genes
    Marker Marker Type Name
    DsRedEFGDsRed
    EGFPEFGEGFP
    1 - 2 of 2
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    No data available
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    Citation
    Wang, Z., Liu, Y., Hu, J., You, X., Yang, J., Zhang, Y., Liu, Q., Yang, D. (2024) Tissue-resident trained immunity in hepatocytes protects against septic liver injury in zebrafish. Cell Reports. 43:114324114324.