DNA methylation and whole-genome transcription analysis in CD4+ T cells from systemic lupus erythematosus patients with or without renal damage

Author:

Liu Xiaomin,Zhou Siyu,Huang Mengjie,Zhao Ming,Zhang Weiguang,Liu Qun,Song Kangkang,Wang Xu,Liu Jiaona,OuYang Qing,Dong Zheyi,Yang Ming,Li Zhenzhen,Lin Li,Liu Yi,Yu Yang,Liao Simin,Zhu Jian,Liu Lin,Li Wenge,Jia Linpei,Zhang Aihua,Guo Chaomin,Yang LiuYang,Li Qing gang,Bai Xueyuan,Li Ping,Cai Guangyan,Lu Qianjin,Chen Xiangmei

Abstract

Abstract Background Lupus nephritis (LN) is the most common cause of kidney injury in systemic lupus erythematosus (SLE) patients and is associated with increased mortality. DNA methylation, one of the most important epigenetic modifications, has been reported as a key player in the pathogenesis of SLE. Hence, our article aimed to explore DNA methylation in CD4+ T cells from LNs to identify additional potential biomarkers and pathogenic genes involved in the progression of LN. Methods Our study enrolled 46 SLE patients with or without kidney injury and 23 healthy controls from 2019 to 2022. CD4+ T cells were sorted for DNA methylation genotyping and RNA-seq. Through bioinformatics analysis, we identified the significant differentially methylated CpG positions (DMPs) only in the LN group and validated them by Bisulfite PCR. Integration analysis was used to screen for differentially methylated and expressed genes that might be involved in the progression of LN, and the results were analyzed via cell experiments and flow cytometry. Results We identified 243 hypomethylated sites and 778 hypermethylated sites only in the LN cohort. Three of these DMPs, cg08332381, cg03297029, and cg16797344, were validated by Bisulfite PCR and could be potential biomarkers for LN. Integrated analysis revealed that the expression of BCL2L14 and IFI27 was regulated by DNA methylation, which was validated by azacytidine (5-aza) treatment. The overexpression of BCL2L14 in CD4+ T cells might induce renal fibrosis and inflammation by regulating the differentiation and function of Tfh cells. Conclusion Our study identified novel aberrant DMPs in CD4+ T cells only in LN patients and DNA methylation-regulated genes that could be potential LN biomarkers. BCL2L14 is likely involved in the progression of LN and might be a treatment target.

Funder

the Young Elite Scientists Sponsorship Program by CAST

National Natural Science Foundation of China

Haihe Laboratory of Cell Ecosystem Innovation Fund

Publisher

Springer Science and Business Media LLC

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