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Published on: February 24, 2023
Tuning Monocytes and Macrophages for Personalized Therapy and Diagnostic Challenge in Rheumatoid Arthritis
Leszek Roszkowski1, Marzena Ciechomska1
1Department of Rheumatology, National Institute of Geriatrics Rheumatology and Rehabilitation, 02-635 Warsaw, Poland.
Abstract:
Monocytes/macrophages play a central role in chronic inflammatory disorders, including rheumatoid arthritis (RA). Activation of these cells results in the production of various mediators responsible for inflammation and RA pathogenesis. On the other hand, the depletion of macrophages using specific antibodies or chemical agents can prevent their synovial tissue infiltration and subsequently attenuates inflammation. Their plasticity is a major feature that helps the switch from a pro-inflammatory phenotype (M1) to an anti-inflammatory state (M2). Therefore, understanding the precise strategy targeting pro-inflammatory monocytes/macrophages should be a powerful way of inhibiting chronic inflammation and bone erosion. In this review, we demonstrate potential consequences of different epigenetic regulations on inflammatory cytokines production by monocytes. In addition, we present unique profiles of monocytes/macrophages contributing to identification of new biomarkers of disease activity or predicting treatment response in RA. We also outline novel approaches of tuning monocytes/macrophages by biologic drugs, small molecules or by other therapeutic modalities to reduce arthritis. Finally, the importance of cellular heterogeneity of monocytes/macrophages is highlighted by single-cell technologies, which leads to the design of cell-specific therapeutic protocols for personalized medicine in RA in the future.
Insights
Targeting pro-inflammatory monocytes/macrophages offers a powerful strategy for inhibiting chronic inflammation and bone erosion in rheumatoid arthritis (RA). Understanding epigenetic regulation and cellular heterogeneity is key to developing effective, personalized RA treatments.
Area of Science:
- Immunology
- Rheumatology
- Molecular Biology
Background:
- Monocytes and macrophages are central to chronic inflammatory disorders like rheumatoid arthritis (RA).
- Their activation drives inflammation and RA pathogenesis, while depletion can reduce synovial infiltration and inflammation.
- Macrophage plasticity allows a switch from pro-inflammatory (M1) to anti-inflammatory (M2) phenotypes.
Purpose of the Study:
- To review epigenetic regulations impacting inflammatory cytokine production by monocytes.
- To present unique monocyte/macrophage profiles for identifying RA biomarkers and predicting treatment response.
- To outline novel therapeutic strategies for modulating monocytes/macrophages to reduce arthritis.
Main Methods:
- Review of literature on epigenetic mechanisms in monocyte/macrophage function.
- Analysis of monocyte/macrophage phenotypes and their role in RA pathogenesis.
- Exploration of therapeutic modalities targeting monocytes/macrophages.
Main Results:
- Epigenetic modifications significantly influence inflammatory cytokine production by monocytes.
- Distinct monocyte/macrophage profiles can serve as biomarkers for RA disease activity and treatment response.
- Various therapeutic approaches, including biologic drugs and small molecules, can modulate monocyte/macrophage activity.
Conclusions:
- Targeting pro-inflammatory monocytes/macrophages is a promising strategy for inhibiting RA-related inflammation and bone erosion.
- Understanding epigenetic regulation and cellular heterogeneity is crucial for developing effective RA therapies.
- Single-cell technologies enable the design of cell-specific therapeutic protocols for personalized RA medicine.
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