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

作　　者：Mengke Chen Yutong Zhang Weiwen Shi Xuejiao Song Yue Yang Guojun Hou Huihua Ding Sheng Chen Wanling Yang Nan Shen Yong Cui Xianbo Zuo Yuanjia Tang 

机构地区：[1]Shanghai Institute of Rheumatology,Renji Hospital,Shanghai Jiao Tong University School of Medicine(SJTUSM),Shanghai 200001,China [2]of Paediatrics and Adolescent Medicine,The University of Hong Kong,Hong Kong 999077,China [3]State Key Laboratory of Oncogenes and Related Genes,Shanghai Cancer Institute,Renji Hospital,Shanghai Jiao Tong University School of Medicine(SJTUSM),Shanghai 200032,China [4]Center for Autoimmune Genomics and Etiology,Cincinnati Children’s Hospital Medical Center,Cincinnati OH 45229,USA [5]Department of Pediatrics,University of Cincinnati College of Medicine,Cincinnati OH 45229,USA [6]Department of Dermatology,China-Japan Friendship Hospital,Beijing 100029,China [7]Department of Pharmacy,China-Japan Friendship Hospital,Beijing 100029,China

出　　处：《Acta Biochimica et Biophysica Sinica》2024年第11期1659-1672,共14页生物化学与生物物理学报(英文版)

基　　金：This work was supported by the grants from the National Natural Science Foundation of China(Nos.82271830,32141004,and 82273523);the Innovative Research Team of High-level Local Universities in Shanghai(No.SHSMU-ZDCX20210600);the National High-Level Hospital Clinical Research Funding(Nos.2022-NHLHCRF-LX-03 and 2023-NHLHCRF-YXHZ-ZRZD-06);the Capital’s Funds for Health Improvement and Research(No.CFH 2020-1-2031).

摘　　要：Through genome-wide association studies(GWAS)and integrated expression quantitative trait locus(eQTL)ana-lyses,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 correlatedwith 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 Iinterferon(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 cyto-metry,we confirm that SPATS2L positively modulates the type I IFN pathway,acting as a positive feedback reg-ulator.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.

关 键 词：systemic lupus erythematosus SPATS2L quantitative trait loci type I interferon 

分 类 号：R595.4[医药卫生—内科学]