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Updated: Nov 20, 2025

Metabolic Characterization of Polarized M1 and M2 Bone Marrow-derived Macrophages Using Real-time Extracellular Flux Analysis
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RNA editing enzyme APOBEC3A promotes pro-inflammatory M1 macrophage polarization

Emad Y Alqassim1,2, Shraddha Sharma3,4, A N M Nazmul H Khan5

  • 1Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, NY, 14203, USA.

Communications Biology
|January 23, 2021
PubMed

Insights

APOBEC3A cytidine deaminase drives M1 macrophage polarization through RNA editing. This process impacts gene expression, cytokine secretion, and cellular metabolism, revealing a key role in immune responses.

Area of Science:

  • Immunology
  • Molecular Biology
  • Virology

Background:

  • Pro-inflammatory M1 macrophage polarization is crucial for microbicidal and antitumor activities.
  • APOBEC3A-mediated cytosine-to-uracil (C>U) RNA editing was previously observed during M1 polarization, but its functional significance remained unclear.

Purpose of the Study:

  • To investigate the functional significance of APOBEC3A-mediated RNA editing in M1 macrophage polarization.
  • To identify the genes and pathways regulated by APOBEC3A during M1 polarization and in response to viral infections.

Main Methods:

  • Gene knockdown of APOBEC3A.
  • RNA sequencing (RNA-Seq) analysis to identify edited sites and gene expression changes.
  • Analysis of cytokine secretion and surface protein expression.
  • Assessment of cellular glycolysis.

Main Results:

  • APOBEC3A-mediated C>U RNA editing occurs in 203 genes during M1 polarization, including THOC5, a nuclear mRNA export protein.
  • APOBEC3A knockdown reduced the expression of key M1-associated genes (IL6, IL23A, IL12B) and cytokines (TNF-α, IL-1β, IL-6).
  • APOBEC3A knockdown also decreased CD86 surface protein expression and increased glycolysis, altering macrophage function.

Conclusions:

  • APOBEC3A plays a critical role in the transcriptomic and functional polarization of M1 macrophages.
  • APOBEC3A-mediated RNA editing is a significant mechanism influencing macrophage-mediated immune responses.
  • APOBEC3A-mediated RNA editing can be induced by viral infections and interferons, highlighting its broader role in innate immunity.

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