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Study on the expression changes of lncRNA in patients with systemic lupus erythematosus and its correlation with Treg cells

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Abstract

Objectives

We initially explored the link between the differentially expressed long non-coding RNAs (lncRNAs) and the number of regulatory T (Treg) cells by detecting the lncRNA expression profiles in patients with systemic lupus erythematosus (SLE), then analyzed the correlation between Treg-related lncRNAs and the clinical features of SLE patients, predicting the mechanism by which lncRNAs regulate the differentiation and development of Treg cells, and provided new ideas for the treatment of SLE.

Methods

Peripheral blood of 9 active SLE patients were collected and mononuclear cells (PBMCs) were extracted; the lncRNA expression profiles of PBMCs were analyzed by whole transcriptome sequencing. Nine healthy people were used as controls to screen the differentially expressed lncRNAs, to analyze the correlation between lncRNAs and Treg cell number. Pearson test was used to analyze the correlation between lncRNAs and the number of Treg cell, and the correlation between Treg-associated lncRNA and SLEDAI score, ESR, C3, and C4 in SLE patients. The targeted genes of Treg-associated lncRNAs were predicted with miRcode and Targetscan databases and coexpression network.

Results

There were 240 differentially expressed lncRNAs in SLE patients compared with healthy controls, including 134 highly expressed lncRNAs (p < 0.05) and 106 lowly expressed lncRNAs (p < 0.05). The expression of ANKRD44-AS1 (r = 0.7417, p = 0.0222), LINC00200 (r = 0.6960, p = 0.0373), AP001363.2 (r = 0.7766, p = 0.0138), and LINC02824 (r = 0.7893, p = 0.0114) were positively correlated with the number of Treg cell, and the expression of AP000640.1 (r = − 0.7225, p = 0.0279), AC124248.1 (r = − 0.7653, p = 0.0163), LINC00482 (r = − 0.8317, p = 0.0054), and MIR503HG (r = − 0.7617, p < 0.05) were negatively correlated with the number of Treg cell. Among these Treg-associated lncRNAs, the expression of LINC00482 (r = − 0.7348, p < 0.05) and MIR503 HG (r = − 0.7617, p < 0.05) were negatively correlated with C3. LINC00200, ANKRD44 - AS1, and AP000640.1 related to Treg cells regulate the expression of signal transducer and activator of transcription 5 (STAT5), phospholipase D1 (PLD1), homeodomain-only protein X (HOPX), and runt-related transcription factor 3 (RUNX3) through competitive binding of miRNA or trans-regulatory mechanism, thereby regulating the differentiation and development of Treg cell.

Conclusions

The lncRNA expression profiles were changed in SLE patients, the differentially expressed lncRNAs were associated with abnormal number and function of Treg cells in SLE, and Treg-associated lncRNAs were associated with SLE-disease activity, which may affect the expression of STAT5, PLD1, HOPX, RUNX3 and regulate Treg cell function and participate in the pathogenesis and progression of SLE by competitively binding to miRNAs or trans-regulatory mechanism.

Key points

• Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organs and systems. lncRNAs may affect Treg cells function by regulating genes expression, which may be an important pathogenesis of SLE.

• This study, taking SLE as an example, preliminarily analyzed the correlation between lncRNA and Treg cells in SLE patients, analyzed the correlation between Treg-related lncRNA and the clinical characteristics of SLE, and speculated that lncRNA could regulate the differentiation and development of Treg cells through competitive combination with miRNA or trans-regulatory mechanisms.

• It is possible to target epigenetic therapy for SLE.

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Acknowledgements

We thank the patients who participated in the study, the Department of Science and Technology of Shanxi Province for supporting the study, the doctors and nurses from the Rheumatology and Immunology Department of the Second Affiliated Hospital of Shanxi Medical University for their support and help, and each author for their help and guidance.

Funding

The Science and Technology Department of Shanxi Province, Grant/Award Number: 20210302123275.

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Author notes

  1. Yu-jie Bu and Xing Cen contributed equally to this work.

Authors and Affiliations

  1. Department of Rheumatology and Immunology, the Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, 030001, People’s Republic of China

    Yu-jie Bu, Xing Cen, Ru Fan, Fen Zhang, Yu-qing Liu, Jia An, Jun Qiao, Sheng-xiao Zhang & Jun-wei Chen

  2. Department of Rheumatology and Immunology, Xi’an No.3 Hospital, the Affiliated Hospital of Northwest University, Xi’an, Shaanxi, 710018, People’s Republic of China

    Yi-qi Wang

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  1. Yu-jie Bu
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Contributions

Chen Junwei, Wang Yiqi, and Zhang Shengxiao conceived the initial idea and project planning. Wang Yiqi, Fan Ru, and An Jia participated in the research design. Yujie Bu and Wang Yiqi collected clinical patient data. Bu Yujie, Cen Xing, and Zhang Fen carried out laboratory work. Bu Yujie, Qiao Jun, Fan Ru, and Liu Yuqing analyzed these data. Bu Yujie, Cen Xing, Wang Yiqi, and Chen Junwei drafted the manuscript.

Corresponding author

Correspondence to Jun-wei Chen.

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Ethics approval

The studies involving human participants were reviewed and approved by the Ethics Committee of the Second Hospital of Shanxi Medical University. The patients/participants provided their written informed consent to participate in this study.

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The authors declare no competing interests.

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Bu, Yj., Cen, X., Wang, Yq. et al. Study on the expression changes of lncRNA in patients with systemic lupus erythematosus and its correlation with Treg cells. Clin Rheumatol 43, 993–1002 (2024). https://doi.org/10.1007/s10067-023-06844-w

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  • DOI: https://doi.org/10.1007/s10067-023-06844-w

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