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Bcl3 Deficiency Leads to Hyperinflammation in Zebrafish.

Chengjian Fan1, Nana Ai1,2, Wei Ge1,2

  • 1Department of Biomedical Sciences, Faculty of Health Sciences, University of Macau, Avenida da Universidade, Taipa, Macau SAR, China.

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|December 24, 2025
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Summary

B-cell leukemia/lymphoma protein 3 (Bcl3) deficiency in zebrafish impairs immune homeostasis, causing reduced survival and increased susceptibility to infections. Restoring immune balance with dexamethasone improved outcomes, revealing Bcl3

Keywords:
Bcl3NF-κB signalinginfectioninflammationzebrafish model

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Area of Science:

  • Immunology
  • Molecular Biology
  • Zebrafish Model Systems

Background:

  • B-cell leukemia/lymphoma protein 3 (Bcl3) is an IκB family protein regulating NF-κB transcription factors.
  • Aberrant Bcl3 activity is linked to various cancers, but its role in immune homeostasis is unclear.

Purpose of the Study:

  • To investigate the physiological function of Bcl3 in immune regulation using a zebrafish model.
  • To elucidate Bcl3's role in maintaining immune homeostasis and organismal survival.

Main Methods:

  • Generation and analysis of Bcl3 knockout zebrafish.
  • Histological examination of immune organs (thymus, liver).
  • Assessment of immune responses and susceptibility to bacterial/viral infections.
  • Measurement of pro-inflammatory cytokine levels (il1b, il6, il8, tnfa).
  • Evaluation of treatment with dexamethasone (Dex).

Main Results:

  • Bcl3 deficient zebrafish showed growth retardation and reduced survival.
  • Absence of Hassall bodies and hepatocellular abnormalities indicated immune organ compromise.
  • Enhanced immune responses, increased infection susceptibility, and elevated pro-inflammatory cytokines were observed.
  • Dexamethasone treatment reduced inflammation, downregulated cytokines, and improved survival.

Conclusions:

  • Bcl3 is a critical regulator of immune activation in vivo.
  • Bcl3 plays a vital role in maintaining immune homeostasis and promoting survival.
  • Targeting Bcl3 pathways may offer therapeutic potential for inflammatory conditions.