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Updated: Mar 8, 2026
An Adoptive Transfer Model of Rheumatoid Arthritis in Mice
Published on: June 6, 2025
MicroRNA-155 contributes to enhanced resistance to apoptosis in monocytes from patients with rheumatoid arthritis
Megha Rajasekhar1, Anton M Olsson1, Kathryn J A Steel1
1Centre for Inflammation Biology and Cancer Immunology, Division of Immunology, Infection and Inflammatory Disease, King's College London, United Kingdom.
Abstract:
Monocytes and macrophages are key mediators of inflammation in rheumatoid arthritis (RA). Their persistence at the inflammatory site is likely to contribute to immunopathology. We sought to characterise one mechanism by which persistence may be achieved: resistance to apoptosis and the role of mir-155 in this process. CD14+ monocytes from peripheral blood (PBM) and synovial fluid (SFM) of RA patients were found to be resistant to spontaneous apoptosis relative to PBM from healthy control (HC) individuals. RA SFM were also resistant to anti-Fas-mediated apoptosis and displayed a gene expression profile distinct from HC and RA PBM populations. Gene expression profiling analysis revealed that the differentially expressed genes in RA SFM vs. PBM were enriched for apoptosis-related genes and showed increased expression of the mir-155 precursor BIC. Following identification of potential mir-155 target transcripts by bioinformatic methods, we show increased levels of mature mir-155 expression in RA PBM and SFM vs. HC PBM and a corresponding decrease in SFM of two predicted mir-155-target mRNAs, apoptosis mediators CASP10 and APAF1. Using miR mimics, we demonstrate that mir-155 over-expression in healthy CD14+ cells conferred resistance to spontaneous apoptosis, but not Fas-induced death in these cells, and resulted in increased production of cytokines and chemokines. Collectively our data indicate that CD14+ cells from patients with RA show enhanced resistance to apoptosis, and suggest that an increase in mir-155 may partially contribute to this phenotype.
Insights
Monocytes in rheumatoid arthritis (RA) resist apoptosis, partly due to increased microRNA-155 (miR-155). This resistance promotes inflammation persistence in RA patients.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- Monocytes and macrophages are central to rheumatoid arthritis (RA) inflammation.
- Their persistence at inflammatory sites contributes to disease pathology.
- Mechanisms of cell persistence, such as apoptosis resistance, are crucial to understand.
Purpose of the Study:
- To investigate apoptosis resistance in monocytes from RA patients.
- To determine the role of microRNA-155 (miR-155) in this resistance.
- To characterize the distinct gene expression profile of RA synovial fluid monocytes.
Main Methods:
- Compared apoptosis rates in CD14+ monocytes from RA patients (peripheral blood and synovial fluid) and healthy controls.
- Analyzed gene expression profiles of RA synovial fluid monocytes.
- Quantified miR-155 levels and its target mRNAs (CASP10, APAF1).
- Used miR mimics to study miR-155 effects in healthy cells.
Main Results:
- RA monocytes exhibited resistance to spontaneous and Fas-mediated apoptosis.
- RA synovial fluid monocytes showed a distinct gene expression profile, enriched for apoptosis-related genes and increased BIC (miR-155 precursor).
- Elevated mature miR-155 levels were found in RA monocytes, correlating with decreased CASP10 and APAF1 mRNA.
- Overexpression of miR-155 in healthy cells induced apoptosis resistance and increased cytokine/chemokine production.
Conclusions:
- CD14+ monocytes from RA patients display enhanced apoptosis resistance.
- Increased miR-155 expression is a potential contributing factor to this phenotype.
- miR-155 may promote RA immunopathology by enhancing monocyte survival and inflammatory mediator release.
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