SPATS2L is a positive feedback regulator of the type I interferon signaling pathway and plays a vital role in lupus
Through genome-wide association studies (GWAS) and integrated expression quantitative trait locus (eQTL) analyses, numerous susceptibility genes (“eGenes”, whose expressions are significantly associated with common variants) associated with systemic lupus erythematosus (SLE) have been identified. No...
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| Format: | Article |
| Language: | English |
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China Science Publishing & Media Ltd.
2024-08-01
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| Series: | Acta Biochimica et Biophysica Sinica |
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| Online Access: | https://www.sciengine.com/doi/10.3724/abbs.2024132 |
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| author | Chen Mengke Zhang Yutong Shi Weiwen Song Xuejiao Yang Yue Hou Guojun Ding Huihua Chen Sheng Yang Wanling Shen Nan Cui Yong Zuo Xianbo Tang Yuanjia |
| author_facet | Chen Mengke Zhang Yutong Shi Weiwen Song Xuejiao Yang Yue Hou Guojun Ding Huihua Chen Sheng Yang Wanling Shen Nan Cui Yong Zuo Xianbo Tang Yuanjia |
| author_sort | Chen Mengke |
| collection | DOAJ |
| description | Through genome-wide association studies (GWAS) and integrated expression quantitative trait locus (eQTL) analyses, numerous susceptibility genes (“eGenes”, whose expressions are significantly associated with common variants) associated with systemic lupus erythematosus (SLE) have been identified. Notably, a subset of these eGenes is correlated with disease activity. However, the precise mechanisms through which these genes contribute to the initiation and progression of the disease remain to be fully elucidated. In this investigation, we initially identify SPATS2L as an SLE eGene correlated with disease activity. eSignaling and transcriptomic analyses suggest its involvement in the type I interferon (IFN) pathway. We observe a significant increase in SPATS2L expression following type I IFN stimulation, and the expression levels are dependent on both the concentration and duration of stimulation. Furthermore, through dual-luciferase reporter assays, western blot analysis, and imaging flow cytometry, we confirm that SPATS2L positively modulates the type I IFN pathway, acting as a positive feedback regulator. Notably, siRNA-mediated intervention targeting SPATS2L, an interferon-inducible gene, in peripheral blood mononuclear cells (PBMCs) from patients with SLE reverses the activation of the interferon pathway. In conclusion, our research highlights the pivotal role of SPATS2L as a positive-feedback regulatory molecule within the type I IFN pathway. Our findings suggest that SPATS2L plays a critical role in the onset and progression of SLE and may serve as a promising target for disease activity assessment and intervention strategies. |
| format | Article |
| id | doaj-art-402003b49c064160aebaa145a314e194 |
| institution | DOAJ |
| issn | 1672-9145 |
| language | English |
| publishDate | 2024-08-01 |
| publisher | China Science Publishing & Media Ltd. |
| record_format | Article |
| series | Acta Biochimica et Biophysica Sinica |
| spelling | doaj-art-402003b49c064160aebaa145a314e1942025-08-20T03:08:00ZengChina Science Publishing & Media Ltd.Acta Biochimica et Biophysica Sinica1672-91452024-08-01561659167210.3724/abbs.202413220d259ccSPATS2L is a positive feedback regulator of the type I interferon signaling pathway and plays a vital role in lupusChen Mengke0Zhang Yutong1Shi Weiwen2Song Xuejiao3Yang Yue4Hou Guojun5Ding Huihua6Chen Sheng7Yang Wanling8Shen Nan9Cui Yong10Zuo Xianbo11Tang Yuanjia12["Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai 200001, China"]["Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai 200001, China"]["Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai 200001, China"]["Department of Dermatology, China-Japan Friendship Hospital, Beijing 100029, China"]["Department of Dermatology, China-Japan Friendship Hospital, Beijing 100029, China","Department of Pharmacy, China-Japan Friendship Hospital, Beijing 100029, China"]["Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai 200001, China"]["Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai 200001, China"]["Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai 200001, China"]["of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong 999077, China"]["Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai 200001, China","State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai 200032, China","Center for Autoimmune Genomics and Etiology, Cincinnati Children’s Hospital Medical Center, Cincinnati OH 45229, USA","Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati OH 45229, USA"]["Department of Dermatology, China-Japan Friendship Hospital, Beijing 100029, China"]["Department of Dermatology, China-Japan Friendship Hospital, Beijing 100029, China","Department of Pharmacy, China-Japan Friendship Hospital, Beijing 100029, China"]["Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai 200001, China"]Through genome-wide association studies (GWAS) and integrated expression quantitative trait locus (eQTL) analyses, numerous susceptibility genes (“eGenes”, whose expressions are significantly associated with common variants) associated with systemic lupus erythematosus (SLE) have been identified. Notably, a subset of these eGenes is correlated with disease activity. However, the precise mechanisms through which these genes contribute to the initiation and progression of the disease remain to be fully elucidated. In this investigation, we initially identify SPATS2L as an SLE eGene correlated with disease activity. eSignaling and transcriptomic analyses suggest its involvement in the type I interferon (IFN) pathway. We observe a significant increase in SPATS2L expression following type I IFN stimulation, and the expression levels are dependent on both the concentration and duration of stimulation. Furthermore, through dual-luciferase reporter assays, western blot analysis, and imaging flow cytometry, we confirm that SPATS2L positively modulates the type I IFN pathway, acting as a positive feedback regulator. Notably, siRNA-mediated intervention targeting SPATS2L, an interferon-inducible gene, in peripheral blood mononuclear cells (PBMCs) from patients with SLE reverses the activation of the interferon pathway. In conclusion, our research highlights the pivotal role of SPATS2L as a positive-feedback regulatory molecule within the type I IFN pathway. Our findings suggest that SPATS2L plays a critical role in the onset and progression of SLE and may serve as a promising target for disease activity assessment and intervention strategies.https://www.sciengine.com/doi/10.3724/abbs.2024132systemic lupus erythematosusSPATS2Lquantitative trait locitype I interferon |
| spellingShingle | Chen Mengke Zhang Yutong Shi Weiwen Song Xuejiao Yang Yue Hou Guojun Ding Huihua Chen Sheng Yang Wanling Shen Nan Cui Yong Zuo Xianbo Tang Yuanjia SPATS2L is a positive feedback regulator of the type I interferon signaling pathway and plays a vital role in lupus Acta Biochimica et Biophysica Sinica systemic lupus erythematosus SPATS2L quantitative trait loci type I interferon |
| title | SPATS2L is a positive feedback regulator of the type I interferon signaling pathway and plays a vital role in lupus |
| title_full | SPATS2L is a positive feedback regulator of the type I interferon signaling pathway and plays a vital role in lupus |
| title_fullStr | SPATS2L is a positive feedback regulator of the type I interferon signaling pathway and plays a vital role in lupus |
| title_full_unstemmed | SPATS2L is a positive feedback regulator of the type I interferon signaling pathway and plays a vital role in lupus |
| title_short | SPATS2L is a positive feedback regulator of the type I interferon signaling pathway and plays a vital role in lupus |
| title_sort | spats2l is a positive feedback regulator of the type i interferon signaling pathway and plays a vital role in lupus |
| topic | systemic lupus erythematosus SPATS2L quantitative trait loci type I interferon |
| url | https://www.sciengine.com/doi/10.3724/abbs.2024132 |
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