Integrative analysis reveals the multilateral inflammatory mechanisms of CD14 monocytes in gout
Authors' conclusion
These findings provide new insights into the role of CD14 monocytes in gout pathogenesis, particularly the contribution of hypoxia and fatty acid metabolism pathways
Study context
- Population
- Gout patients and age- and sex-matched healthy controls; CD14 monocytes from PBMCs
- Participants
- 8 vs 6
- Comparison
- Gout patients vs age- and sex-matched healthy controls
- Goutn = 8
- Healthy controlsn = 6reference
- Outcome
- Molecular and cellular landscape of CD14 monocytes in gout
Methodological detailssingle-cell RNA sequencing, age- and sex-matched healthy controls, validation in publicly available datasets, in vitro monosodium urate crystal stimulation
- Single-cell RNA sequencing
- Age- and sex-matched healthy controls
- Validation in publicly available datasets
- In vitro monosodium urate crystal stimulation
Main finding
As reported in the abstract
- Hypoxia-related pathways, incl. HIF1A, identified as key regulators of IL-1β production in CD14 monocytes in gout
- Significant downregulation of CLEC12A across all CD14 monocyte subclusters
- S100Ahigh CD14 monocyte subcluster (high S100A8/A9/A12; inflammatory and metabolic pathways) drives NLRP3 and CLEC7A inflammasome activation and prostaglandin secretion
- After in vitro monosodium urate crystal stimulation, differentially expressed genes enriched in S100Ahigh monocytes
- Gout GWAS-prioritised genes underscore role of fatty acid metabolism in inflammation, promoting prostaglandin secretion from S100Ahigh monocytes
Original publication
Integrative analysis reveals the multilateral inflammatory mechanisms of CD14 monocytes in gout. Ann Rheum Dis. Published 28 February 2025. doi:10.
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