Lupus & antiphospholipid syndrome
Activin A–Activated ALK4 Induces Pathogenic Th17‐Involved Endothelial–Mesenchymal Transition in Systemic Lupus Erythematosus–Associated Pulmonary Arterial Hypertension
Authors' conclusion
Our findings suggest that Activin A activates ALK4 in Th17 cells, thereby inducing IL-17 secretion. Concurrently, activated ALK4 induces EndoMT in human PMECs (hPMECs) via CTGF up-regulation.
Study context
- Population
- Patients with SLE-PAH, patients with systemic lupus erythematosus (SLE), healthy donors; Th17–PMEC cocultures and SLE-PH mouse models
- Comparison
- SLE-PAH vs SLE only vs healthy donors
Methodological detailsmass cytometry (CyTOF), ELISA, coculture of Th17 cells with pulmonary microvascular endothelial cells (PMECs), rodent models
- Mass cytometry (CyTOF)
- ELISA
- Coculture of Th17 cells with PMECs
- Rodent models
Main finding
As reported in the abstract
- Reduced CD4+ T cell number in SLE-PAH after treatment with immunosuppressant and vasodilator
- Increased Th17 cell population and higher serum Activin A and IL-17 in SLE-PAH vs SLE only or donors
- Activin A signals via ALK4 in both Th17 cells and PMECs
- ALK4 overexpression in Th17 cells increased IL-6 and endothelial-mesenchymal transition (EndoMT) marker levels in cocultured PMECs
- ALK4 overexpression caused severe SLE-PH in mice; CD4+ T cell depletion alleviated hemodynamic changes
- ALK4 inhibitor vactosertib (TEW-7197) effectively treated SLE-PH mice by repressing connective tissue growth factor (CTGF) transcription induced by ALK4-activated pSmad2 and pSTAT3
Original publication
Activin A–Activated ALK4 Induces Pathogenic Th17‐Involved Endothelial–Mesenchymal Transition in Systemic Lupus Erythematosus–Associated Pulmonary Arterial Hypertension. Arthritis Rheumatol. Published 16 July 2025. doi:10.
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