Related Experiment Video
Updated: Jan 13, 2026

An Adoptive Transfer Model of Rheumatoid Arthritis in Mice
Published on: June 6, 2025
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.
Background:
Arthritis is an inflammatory disease characterized by multifactorial pathogenesis in joints or surrounding tissues. M1 macrophage polarization is a key pathological feature of arthritis, and m⁵C RNA modification has been implicated in disease progression. This study aimed to elucidate the role of NSUN2, a writer of m⁵C modification, in modulating arthritis development.
Methods:
LPS-stimulated RAW264.7 cell models and collagen-induced arthritis (CIA) rat models were established. M1 and M2 macrophage polarization was assessed by detecting cell surface markers and pro-inflammatory cytokines using immunofluorescence, enzyme-linked immunosorbent assay (ELISA), Western blot, and quantitative real-time PCR. Underlying mechanisms were investigated via methylated RNA immunoprecipitation (MeRIP), Co-immunoprecipitation (Co-IP), and Dual-Luciferase reporter assays.
Results:
Downregulation of NSUN2 significantly inhibited M1 polarization and promoted M2 activation both in vitro and in vivo. NSUN2 enhanced m5C modification of CCL2, stabilized its mRNA expression, and facilitated its interaction with CCR2. Furthermore, NSUN2 activated the NF-κB signaling pathway in macrophages. Notably, inhibition of CCL2 activity abrogated the effects of NSUN2 on macrophage polarization.
Conclusion:
NSUN2 drives M1 macrophage polarization through m5C modification of CCL2, thereby exacerbating arthritis progression. Targeting NSUN2 may alleviate inflammatory responses, offering a novel therapeutic strategy for arthritis treatment.
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.
More Related Videos
Related Concept Videos
T Cell Types and Functions
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
The JAK-STAT Signaling Pathway

