Irf5 Knockdown in Bone Marrow-Derived Macrophages Favors M1-to-M2 Transition

Elizaveta Petrova1, Ekaterina Sherstyukova2, Snezhanna Kandrashina2

  • 1Odintsovo Center of Medical and Biological Technologies, 143025 Moscow, Russia.

Cells
|February 12, 2026
PubMed

Insights

The transcription factor IRF5 is crucial for maintaining macrophage polarization. Its knockdown alters macrophage phenotypes, impacting their function and metabolic properties.

Area of Science:

  • Immunology
  • Cell Biology

Background:

  • Macrophages are key immune cells with distinct polarization states (M1 and M2).
  • The transcription factor Interferon Regulatory Factor 5 (IRF5) is known to maintain the pro-inflammatory M1 macrophage state.

Purpose of the Study:

  • To investigate the role of IRF5 in macrophage polarization.
  • To assess the effects of IRF5 knockdown on M0, M1, and M2 murine bone marrow-derived macrophages (BMDM).

Main Methods:

  • siRNA-mediated knockdown of Irf5 in BMDM.
  • Phenotypic analysis of macrophage states.
  • Measurement of M1 (iNOS) and M2 (CD206) marker expression.
  • Assessment of mitochondrial content and morphology.
  • Atomic Force Microscopy (AFM) for plasma membrane roughness and stiffness measurements.

Main Results:

  • IRF5 knockdown in M1 macrophages induced an M2-like phenotype, characterized by decreased iNOS and increased CD206 expression.
  • IRF5 reduction also affected the M2 macrophage phenotype.
  • IRF5 knockdown increased plasma membrane roughness and altered macrophage elasticity, particularly in M2 cells.
  • IRF5 plays a complex role in regulating macrophage polarization and associated functional properties.

Conclusions:

  • IRF5 has a dual role in macrophage polarization, acting as both a transcriptional activator and repressor.
  • IRF5 is essential for maintaining the metabolic and functional characteristics of macrophages in both M1 and M2 states.

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