SPATS2L is a positive feedback regulator of the type I interferon signaling pathway and plays a vital role in lupus

被引:0
作者
Chen, Mengke [1 ]
Zhang, Yutong [1 ]
Shi, Weiwen [1 ]
Song, Xuejiao [6 ]
Yang, Yue [6 ,7 ]
Hou, Guojun [1 ]
Ding, Huihua [1 ]
Chen, Sheng [1 ]
Yang, Wanling [2 ]
Shen, Nan [1 ,3 ,4 ,5 ]
Cui, Yong [6 ]
Zuo, Xianbo [6 ,7 ]
Tang, Yuanjia [1 ]
机构
[1] Shanghai Jiao Tong Univ, Renji Hosp, Shanghai Inst Rheumatol, Sch Med SJTUSM, Shanghai 200001, Peoples R China
[2] Univ Hong Kong, Dept Paediat & Adolescent Med, Hong Kong 999077, Peoples R China
[3] Shanghai Jiao Tong Univ, Renji Hosp, State Key Lab Oncogenes & Related Genes, Shanghai Canc Inst,Sch Med SJTUSM, Shanghai 200032, Peoples R China
[4] Cincinnati Childrens Hosp Med Ctr, Ctr Autoimmune Genom & Etiol, Cincinnati, OH 45229 USA
[5] Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH 45229 USA
[6] China Japan Friendship Hosp, Dept Dermatol, Beijing 100029, Peoples R China
[7] China Japan Friendship Hosp, Dept Pharm, Beijing 100029, Peoples R China
基金
中国国家自然科学基金;
关键词
systemic lupus erythematosus; SPATS2L; quantitative trait loci; type I interferon; GENOME-WIDE ASSOCIATION; INDUCIBLE GENE-EXPRESSION; RHEUMATOID-ARTHRITIS; SUSCEPTIBILITY LOCI; DISEASE-ACTIVITY; ERYTHEMATOSUS; CHINESE; RISK; IDENTIFICATION; SCHIZOPHRENIA;
D O I
10.3724/abbs.2024132
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:1659 / 1672
页数:14
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