Positive feedback loop PU.1-IL9 in Th9 promotes rheumatoid arthritis development
Authors' conclusion
These results support that the PU.1-IL-9 axis forms a positive loop in Th9 dysregulation of RA.
Study context
- Population
- Patients with RA; PU.1-T cell-conditional knockout (KO), IL-9 KO and IL-9R KO mice (collagen antibody-induced arthritis (CAIA)); Collagen-induced arthritis (CIA) mice
Methodological detailshuman samples, conditional knockout mouse models, CAIA and CIA models, in vitro assays
- Human samples
- Conditional knockout mouse models
- CAIA and CIA models
- In vitro assays
Main finding
As reported in the abstract
- Upregulated IL-9 expression in patients with RA correlated positively with clinical markers
- Interventions targeting PU.1 and IL-9 substantially mitigated the inflammatory phenotype in CAIA and CIA models
- IL-9 proinflammatory in vitro, particularly in hyperactivation of macrophages and fibroblast-like synoviocytes
- PU.1 directly binds the IL-9 promoter, activating its transcription
- Th9-derived IL-9 induces PU.1 via the IL-9R-JAK1/STAT3 pathway (positive feedback loop)
Original publication
Positive feedback loop PU.1-IL9 in Th9 promotes rheumatoid arthritis development. Ann Rheum Dis. Published 14 November 2024. doi:10.
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