OBJECTIVES: Plasmacytoid dendritic cells (pDCs), through the production of type 
1 interferons (IFNs) and other cytokines, are major contributors to systemic 
lupus erythematosus (SLE) pathogenesis. IL-3 promotes pDC survival, but its role 
in SLE is not well characterised. This study investigated serum IL-3 and IFN 
levels, and a whole blood 'IL-3 gene signature', in human SLE.
METHODS: Serum cytokine levels were measured by ELISA in n = 42 SLE patients, 
and n = 44 healthy donors. IL-3-regulated genes were determined by RNASeq of 
healthy donor whole blood cells (WBCs) stimulated in vitro with IL-3 for 6 or 
24 h. Whole blood cell RNASeq analysis was undertaken in a separate cohort of 
n = 31 SLE patients, and n = 28 healthy donors.
RESULTS: Serum IL-3 levels correlated with IFNα (r = 0.612, 95% CI 0.455-0.733, 
P < 0.001) and type III IFN (r = 0.585, 95% CI 0.406-0.720, P < 0.0001). IL-3 
stimulation of WBC in vitro altered 794 genes (-1 ≥ logFC ≥ 1, FDR < 0.05), of 
which 35 overlapped with genes differentially expressed between SLE and healthy 
donors. These 35 genes were expressed in 27/31 SLE donors, revealing the 
presence of an 'IL-3 gene signature'. There was strong correlation between the 
IL-3 signature and an IFN signature, as determined by hierarchical clustering of 
the 500 most variable genes in SLE donors (r = 0.939, 95% CI 0.898-0.964, 
P < 0.0001).
CONCLUSION: A dual IL-3/IFN gene signature is a feature of SLE. An association 
between IL-3 and IFN raises the possibility that dual blockade of IL-3 and IFN 
may be especially useful for SLE patients with this dual cytokine gene 
signature.