NSUN2 aggravates M1 macrophage polarization in arthritis progression through m5C modification of CCL2

Chunlei He1, Junhua Zhang2, Geer Deli2

  • 1Department of Orthopedics, The First Affiliated Hospital of Gannan Medical University, Ganzhou, China; Ganzhou Key Laboratory of Artificial Joints Research, Ganzhou, China.

Molecular Immunology
|January 8, 2026
PubMed
Abstract

Insights

NSUN2 drives M1 macrophage polarization via m5C modification of CCL2, worsening arthritis. Targeting NSUN2 may reduce inflammation and offer a new arthritis treatment strategy.

Area of Science:

  • Immunology
  • Molecular Biology
  • RNA Epigenetics

Background:

  • Arthritis involves joint inflammation and M1 macrophage polarization.
  • m5C RNA modification is linked to arthritis progression.
  • NSUN2, an m5C writer, is investigated for its role in arthritis.

Purpose of the Study:

  • To elucidate the role of NSUN2 in modulating arthritis development.
  • To investigate how NSUN2 influences macrophage polarization in arthritis.
  • To explore NSUN2 as a potential therapeutic target for arthritis.

Main Methods:

  • Utilized LPS-stimulated RAW264.7 cells and collagen-induced arthritis (CIA) rat models.
  • Assessed macrophage polarization markers and cytokines via immunofluorescence, ELISA, Western blot, and qPCR.
  • Investigated molecular mechanisms using MeRIP, Co-IP, and Dual-Luciferase reporter assays.

Main Results:

  • NSUN2 downregulation inhibited M1 polarization and promoted M2 activation in vitro and in vivo.
  • NSUN2 enhanced CCL2 mRNA m5C modification, stabilizing its expression and facilitating CCR2 interaction.
  • NSUN2 activated the NF-κB pathway in macrophages; CCL2 inhibition abrogated NSUN2's effects.

Conclusions:

  • NSUN2 promotes M1 macrophage polarization by m5C modifying CCL2, exacerbating arthritis.
  • Targeting NSUN2 may alleviate inflammatory responses in arthritis.
  • NSUN2 presents a novel therapeutic strategy for arthritis treatment.