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Updated: May 17, 2025

Characterization of Thymus-dependent and Thymus-independent Immunoglobulin Isotype Responses in Mice Using Enzyme-linked Immunosorbent Assay
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eIF3a function in immunity and protection against severe sepsis by regulating B cell quantity and function through

Qianying Ouyang1,2,3,4,5, Jiajia Cui1,2,3,4,6,7, Yang Wang8

  • 1Department of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Xiangya Hospital, Central South University, Changsha 410008, China.

Acta Pharmaceutica Sinica. B
|May 15, 2025
PubMed

Insights

eIF3a protein is crucial for a healthy immune system and preventing sepsis. Its deficiency causes organ damage, but restoring eIF3a levels protects against sepsis by regulating B cells.

Area of Science:

  • Molecular Biology
  • Immunology
  • RNA Biology

Background:

  • The protein eIF3a acts as a reader for N6-methyladenosine (m6A) modifications on messenger RNAs (mRNAs).
  • eIF3a is hypothesized to regulate mRNA translation, particularly during infection when cap-dependent initiation is impaired.
  • Understanding the in vivo function of eIF3a in immunity is limited due to challenges in animal model studies.

Purpose of the Study:

  • To investigate the in vivo function of eIF3a in the context of immunity and sepsis.
  • To elucidate the role of eIF3a in regulating immune responses and organ damage.

Main Methods:

  • Utilized eIF3a knockout and knockdown mouse models.
  • Induced sepsis using Lipopolysaccharide (LPS) challenge.
  • Assessed organ damage, splenic tissue integrity, and B cell function and quantity.

Main Results:

  • eIF3a deficiency led to splenic tissue disruption and multi-organ damage, exacerbating LPS-induced sepsis.
  • Overexpression of eIF3a in knockdown mice rescued them from severe sepsis.
  • eIF3a regulates B cell function and quantity via m6A modification of mRNAs, maintaining immune health.

Conclusions:

  • eIF3a plays a critical role in maintaining immune system health and preventing sepsis.
  • eIF3a regulates B cell homeostasis through m6A-dependent mRNA mechanisms.
  • eIF3a represents a potential therapeutic target for sepsis treatment.
Keywords:
B cellHumoral immunityInfectionRNA modificationSepsisTranslational regulationeIF3am6A

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