A potential association between IL-3 and type I and III interferons in systemic lupus erythematosus

Oon, S; Monaghan, K; Ng, M; Hoi, A; Morand, E; Vairo, G; Maraskovsky, E; Nash, AD; Wicks, IP; Wilson, NJ

Author(s): Oon, S; Monaghan, K; Ng, M; Hoi, A; Morand, E; Vairo, G; Maraskovsky, E; Nash, AD; Wicks, IP; Wilson, NJ;
Details: Publication Year 2019,Volume 8,Issue #12,Page e01097
Journal Title: Clin Transl Immunology
Publication Type: Journal Article
Abstract: 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 IFNalpha (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.
Publisher: Wiley
Research Division(s): Inflammation
PubMed ID: 31890206
Link To PubMed Central Version: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928763/
Publisher's Version: https://doi.org/10.1002/cti2.1097
NHMRC Grants: NHMRC/1023407, NHMRC/1016647, NHMRC/1039026,
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2020-01-21 11:05:26

Last Modified: 2020-02-10 05:14:00