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Updated: Mar 13, 2026
An Adoptive Transfer Model of Rheumatoid Arthritis in Mice
Published on: June 6, 2025
Lnc-CHRM4-2:1 Inhibits M2 Polarization and Efferocytosis of Macrophages by Downregulating MerTK and SLC2A1 in
Jinjin Chu1, Jie Zang1, Lili Zhang1
1Medical Research Center, Weifang People's Hospital, Shandong Second Medical University, Weifang, 261000, China, wfph.cn.
Objective:
Rheumatoid arthritis (RA) is a common chronic and systemic autoimmune disease. Long noncoding RNAs (lncRNAs) have been documented to play important roles in the pathogenesis of RA. This study is aimed to investigate the differentially expressed lncRNAs in RA and explore the underlying roles and mechanisms of RA-specific lncRNAs.
Methods:
Peripheral blood mononuclear cells (PBMCs) from three RA patients and three healthy controls were detected by transcriptome sequencing analysis. Enrichment analysis was performed to identify the potential functional categories and signal pathways. The expressions of the screened dysregulated lncRNAs in RA were further validated using quantitative real-time polymerase chain reaction (qRT-PCR). The effects of the candidate lncRNA lnc-CHRM4-2:1 on the proliferation and apoptosis of Raw264.7 cells were determined by cell counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) proliferation assays, and Annexin V-APC/PI staining flow cytometry assay. qRT-PCR and western blot were performed to detect the expression of functional molecules related to M1/M2 macrophage polarization and efferocytosis.
Results:
The expression of lnc-CHRM4-2:1 was significantly higher in PBMCs of RA patients compared to healthy controls. Lnc-CHRM4-2:1 was negatively associated with the level of serum CCP of RA patients, suggesting that it was a RA-specific lncRNA. Overexpression of lnc-CHRM4-2:1 could potentially affect cell proliferation and apoptosis, promote M1 polarization, inhibit M2 polarization, and the mRNA and protein expressions of MerTK and SLC2A1 in Raw264.7 cells.
Conclusion:
Lnc-CHRM4-2:1 is an RA-specific lncRNA, which inhibits macrophage M2 polarization and efferocytosis by downregulating MerTK and SLC2A1. Lnc-CHRM4-2:1 may be considered a potential diagnostic biomarker and therapeutic target for RA.
Insights
This study identified lnc-CHRM4-2:1 as a rheumatoid arthritis (RA)-specific long noncoding RNA. It inhibits M2 macrophage polarization and efferocytosis, suggesting its potential as a diagnostic biomarker and therapeutic target for RA.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- Rheumatoid arthritis (RA) is a chronic autoimmune disease where long noncoding RNAs (lncRNAs) play a role in its pathogenesis.
- Understanding the specific lncRNAs involved in RA is crucial for developing new diagnostic and therapeutic strategies.
Purpose of the Study:
- To investigate differentially expressed lncRNAs in rheumatoid arthritis (RA).
- To explore the roles and mechanisms of RA-specific lncRNAs in disease development.
Main Methods:
- Transcriptome sequencing of peripheral blood mononuclear cells (PBMCs) from RA patients and healthy controls.
- Quantitative real-time polymerase chain reaction (qRT-PCR) for lncRNA validation.
- Cell-based assays (CCK-8, EdU, flow cytometry) to assess the functional impact of lnc-CHRM4-2:1 on macrophage polarization and efferocytosis.
Main Results:
- Lnc-CHRM4-2:1 expression was significantly elevated in RA patients' PBMCs and negatively correlated with serum CCP levels, indicating its specificity to RA.
- Overexpression of lnc-CHRM4-2:1 affected cell proliferation and apoptosis, promoted M1 macrophage polarization, inhibited M2 polarization, and downregulated MerTK and SLC2A1 expression.
Conclusions:
- Lnc-CHRM4-2:1 is identified as an RA-specific lncRNA.
- It inhibits M2 macrophage polarization and efferocytosis by downregulating MerTK and SLC2A1.
- Lnc-CHRM4-2:1 shows potential as a diagnostic biomarker and therapeutic target for rheumatoid arthritis.
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