AI Article Synopsis
- Behçet's disease (BD) is a systemic vasculitis characterized by inflammation driven by certain immune cells, and the drug apremilast has been approved as a treatment.
- Research involved analyzing neutrophil activity in BD patients, revealing that their immune cells showed increased activation and dysfunction compared to healthy individuals.
- Apremilast significantly reduced these harmful neutrophil activities, suggesting its potential to improve immune regulation in BD patients.
Article Abstract
Objective: Behçet's disease (BD) is a systemic vasculitis with inflammatory lesions mediated by cytotoxic T cells and neutrophils. Apremilast, an orally available small-molecule drug that selectively inhibits phosphodiesterase 4 (PDE4), has been recently approved for the treatment of BD. We aimed to investigate the effect of PDE4 inhibition on neutrophil activation in BD.
Methods: We studied surface markers and reactive oxygen species (ROS) production by flow cytometry, and neutrophil extracellular traps (NETs) production and molecular signature of neutrophils by transcriptome analysis before and after PDE4 inhibition.
Results: Activation surface markers (CD64, CD66b, CD11b, and CD11c), ROS production, and NETosis were up-regulated in BD patient neutrophils compared to healthy donor neutrophils. Transcriptome analysis revealed 1,021 significantly dysregulated neutrophil genes between BD patients and healthy donors. Among dysregulated genes, we found a substantial enrichment for pathways linked to innate immunity, intracellular signaling, and chemotaxis in BD. Skin lesions of BD patients showed increased infiltration of neutrophils that colocalized with PDE4. Inhibition of PDE4 by apremilast strongly inhibited neutrophil surface activation markers as well as ROS production, NETosis, and genes and pathways related to innate immunity, intracellular signaling, and chemotaxis.
Conclusion: We highlight key biologic effects of apremilast on neutrophils in BD.
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| http://dx.doi.org/10.1002/art.42486 | DOI Listing |
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