A potential association between IL‐3 and type I and III interferons in systemic lupus erythematosus
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 investiga...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Clinical & Translational Immunology |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cti2.1097 |
| _version_ | 1818032485890523136 |
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| author | Shereen Oon Katherine Monaghan Milica Ng Alberta Hoi Eric Morand Gino Vairo Eugene Maraskovsky Andrew D Nash Ian P Wicks Nicholas J Wilson |
| author_facet | Shereen Oon Katherine Monaghan Milica Ng Alberta Hoi Eric Morand Gino Vairo Eugene Maraskovsky Andrew D Nash Ian P Wicks Nicholas J Wilson |
| author_sort | Shereen Oon |
| collection | DOAJ |
| description | 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 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. |
| first_indexed | 2024-12-10T06:08:08Z |
| format | Article |
| id | doaj.art-dc33ae9259a9457d941114886e24feff |
| institution | Directory Open Access Journal |
| issn | 2050-0068 |
| language | English |
| last_indexed | 2024-12-10T06:08:08Z |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical & Translational Immunology |
| spelling | doaj.art-dc33ae9259a9457d941114886e24feff2022-12-22T01:59:39ZengWileyClinical & Translational Immunology2050-00682019-01-01812n/an/a10.1002/cti2.1097A potential association between IL‐3 and type I and III interferons in systemic lupus erythematosusShereen Oon0Katherine Monaghan1Milica Ng2Alberta Hoi3Eric Morand4Gino Vairo5Eugene Maraskovsky6Andrew D Nash7Ian P Wicks8Nicholas J Wilson9The Walter and Eliza Hall Institute of Medical Research Parkville VIC AustraliaCSL Limited Parkville VIC AustraliaCSL Limited Parkville VIC AustraliaMonash University Melbourne VIC AustraliaMonash University Melbourne VIC AustraliaCSL Limited Parkville VIC AustraliaThe University of Melbourne Parkville VIC AustraliaThe University of Melbourne Parkville VIC AustraliaThe Walter and Eliza Hall Institute of Medical Research Parkville VIC AustraliaThe University of Melbourne Parkville VIC AustraliaAbstract 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.https://doi.org/10.1002/cti2.1097cytokinesgene signatureimmunological disordersinterferonsinterleukin-3systemic lupus erythematosus |
| spellingShingle | Shereen Oon Katherine Monaghan Milica Ng Alberta Hoi Eric Morand Gino Vairo Eugene Maraskovsky Andrew D Nash Ian P Wicks Nicholas J Wilson A potential association between IL‐3 and type I and III interferons in systemic lupus erythematosus Clinical & Translational Immunology cytokines gene signature immunological disorders interferons interleukin-3 systemic lupus erythematosus |
| title | A potential association between IL‐3 and type I and III interferons in systemic lupus erythematosus |
| title_full | A potential association between IL‐3 and type I and III interferons in systemic lupus erythematosus |
| title_fullStr | A potential association between IL‐3 and type I and III interferons in systemic lupus erythematosus |
| title_full_unstemmed | A potential association between IL‐3 and type I and III interferons in systemic lupus erythematosus |
| title_short | A potential association between IL‐3 and type I and III interferons in systemic lupus erythematosus |
| title_sort | potential association between il 3 and type i and iii interferons in systemic lupus erythematosus |
| topic | cytokines gene signature immunological disorders interferons interleukin-3 systemic lupus erythematosus |
| url | https://doi.org/10.1002/cti2.1097 |
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