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Updated: Feb 24, 2026
An Adoptive Transfer Model of Rheumatoid Arthritis in Mice
Published on: June 6, 2025
MiR-let-7a regulates anti-citrullinated protein antibody-induced macrophage activation and correlates with the
Wei Zhu1, Jianbo Yu2, Shou Qiu1
1Department of Immunology, Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, China; Key Laboratory of Tumor Prevention and Treatment of Heilongjiang Province, Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, China.
Abstract:
Anti-citrullinated protein antibodies (ACPAs) are a key serological marker of rheumatoid arthritis (RA). To investigate whether miR-let7a downregulated ACPA-induced macrophage activation and arthritis, miR-let7a levels were assessed in the synovial fluid from patients with RA or osteoarthritis (OA). In addition, expression of the pro-inflammatory genes HMGA2, PI3K, and IRF5 was examined in ACPA-induced macrophages and a collagen antibody-induced mouse model of arthritis. As expected, miR-let7a expression in synovial fluid macrophages was substantially lower in patients with RA than in those with OA. Moreover, ACPAs treatment (160IU/mL) suppressed miR-let7a expression in macrophages isolated from patients with RA. Mechanistic studies revealed that miR-let7a directly targets HMGA2 to suppress ACPA-induced IRF5 expression through PI3K in macrophages. Further, miR-let7a expression was markedly decreased in swollen ankle tissue and splenocytes isolated from arthritic mice, whereas HMGA2, PI3K, and IRF5 expression positively correlated with disease severity. However, injection miR-let7a agomir was unable to mitigate the development of experimental arthritis in model mice. Collectively, these data demonstrated that miR-let7a directly targets HMGA2 to downregulate ACPAs-induced macrophage activation, and correlated with experimental RA severity.
Insights
MicroRNA let-7a (miR-let7a) downregulation in rheumatoid arthritis (RA) correlates with disease severity. While miR-let7a targets HMGA2 to reduce macrophage activation in RA, it did not mitigate experimental arthritis in mice.
Area of Science:
- Immunology
- Molecular Biology
- Rheumatology
Background:
- Anti-citrullinated protein antibodies (ACPAs) are critical biomarkers for rheumatoid arthritis (RA).
- Macrophage activation plays a significant role in RA pathogenesis.
- The role of microRNAs, specifically miR-let7a, in ACPA-mediated RA is not fully understood.
Purpose of the Study:
- To investigate the role of miR-let7a in ACPA-induced macrophage activation and experimental arthritis.
- To determine the relationship between miR-let7a levels and RA disease severity.
- To elucidate the molecular targets of miR-let7a in the context of RA.
Main Methods:
- Assessed miR-let7a levels in synovial fluid from RA and osteoarthritis (OA) patients.
- Examined gene expression (HMGA2, PI3K, IRF5) in ACPA-treated macrophages and an arthritis mouse model.
- Utilized mechanistic studies to identify miR-let7a targets and pathways.
- Administered miR-let7a agomir to arthritic mice to assess therapeutic potential.
Main Results:
- miR-let7a expression was significantly lower in RA patients' synovial fluid macrophages compared to OA patients.
- ACPA treatment suppressed miR-let7a in RA macrophages.
- miR-let7a directly targets HMGA2, suppressing ACPA-induced IRF5 expression via PI3K.
- Decreased miR-let7a and increased HMGA2, PI3K, IRF5 correlated with arthritis severity in mice.
- miR-let7a agomir injection failed to ameliorate experimental arthritis.
Conclusions:
- miR-let7a directly targets HMGA2 to downregulate ACPA-induced macrophage activation.
- miR-let7a levels correlate with experimental rheumatoid arthritis severity.
- Therapeutic strategies targeting miR-let7a may require further refinement for RA treatment.
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