ORIGINAL RESEARCH article
Front. Immunol.
Sec. Systems Immunology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1580540
Multi-omics Integration Identifies NK Cell-Mediated Cytotoxicity as a Therapeutic Target in Systemic Lupus Erythematosus
Provisionally accepted
- 1Nanjing Drum Tower Hospital, Nanjing, China
- 2Ningbo First Hospital, Ningbo, Zhejiang Province, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Background: Systemic lupus erythematosus (SLE) is an autoimmune condition that impacts various organs. Given the intricate clinical progression of SLE, it is imperative to explore novel avenues for precise diagnosis and treatment.Methods: Peripheral blood mononuclear cells (PBMC) were isolated from 6 SLE patients before and after treatment, 7 healthy controls and 7 disease controls. Assay for Transposase Accessible Chromatin with high throughput Sequencing (ATAC-seq) was used to analyze the chromatin accessibility signatures and RNA-seq was used to identify the differentially expressed genes, mRNA, lncRNA, circRNA, miRNA. Then ATAC-seq and RNA-seq were integrated to further analyze hub genes and pathways.Finally, we validated gene expression levels and examined changes in key genes after treatment through in vitro experiments.Results: Our analysis reveals dynamic changes in chromatin accessibility during the course of disease progression in SLE. Significantly higher numbers of differentially accessible regions, transcripts, genes, mRNA, lncRNA, circRNA, and miRNA were observed in SLE patients compared to other cohorts, with these variances markedly reduced post-treatment. Two gene clusters associated with SLE disease improvement were identified, with a total of 140 genes intersecting with ATAC results. Pathway analysis revealed that NK cell mediated cytotoxicity was the most differentiated and therapeutically altered pathway in SLE patients. Independent sample validation confirmed that the gene expression of this pathway was reduced in SLE patients and associated with disease activity, whereas hydroxychloroquine (HCQ) effectively elevated their expression in vitro.Our findings suggest that these NK cell signature genes may be associated with the complex pathogenesis of SLE. The restoration of NK cell-mediated cytotoxicity may serve as a useful marker of improvement following SLE treatment.
Keywords: systemic lupus erythematosus, ATAC-seq, RNA-Seq, NK cells, Open chromatin
Received: 20 Feb 2025; Accepted: 18 Apr 2025.
Copyright: © 2025 Zhang, Ma, Deng, Yi, Tohtihan, Tang, Wu and Feng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Xiudi Wu, Ningbo First Hospital, Ningbo, 315016, Zhejiang Province, China
Xuebing Feng, Nanjing Drum Tower Hospital, Nanjing, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.