International Journal of General Medicine (Aug 2023)

TRIM5 Promotes Systemic Lupus Erythematosus Through CD4(+) T Cells and Macrophage

  • Pan Z,
  • Yang Q,
  • Zhang X,
  • Xu X,
  • Sun Y,
  • Zhou F,
  • Wen L

Journal volume & issue
Vol. Volume 16
pp. 3567 – 3580

Abstract

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Zhaobing Pan,1– 3,* Qiaoshan Yang,1– 3,* Xiaojing Zhang,1– 3 Xiaoqing Xu,1– 3 Yao Sun,1– 3 Fusheng Zhou,1– 4 Leilei Wen1– 3 1Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Institute of Dermatology, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 3Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei, Anhui, People’s Republic of China; 4Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, Anhui, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fusheng Zhou; Leilei Wen, Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, No. 218, Jixi Road, Shushan District, Hefei, 230000, Anhui, People’s Republic of China, Tel +86-138-5698-5934 ; +86-183-5609-9275, Fax +86-0551-63633742, Email [email protected]; [email protected]: Systemic lupus erythematosus (SLE) is a typical autoimmune disease characterized by the involvement of multiple organs and the production of antinuclear antibodies. This study aimed to investigate the molecular mechanism of SLE.Patients and Methods: We retrieved genome-wide gene expression levels from five public datasets with relatively large sample sizes from the Gene Expression Omnibus (GEO), and we compared the expression profiles of peripheral blood mononuclear cells (PBMCs) from SLE patients and healthy controls (HCs). The expression of seven target genes in PBMCs from 25 cases and 3 HCs was further validated by reverse-transcription quantitative PCR (RT‒qPCR). Flow cytometry was used for verifying the proportion of naive CD4(+) T cells and M2 macrophages in PBMCs from 5 cases and 4 HCs.Results: We found 14 genes (TRIM5, FAM8A1, SHFL, LHFPL2, PARP14, IFIT5, PARP12, DDX60, IRF7, IF144, OAS1, OAS3, RHBDF2, and RSAD2) that were differentially expressed among all five datasets. The heterogeneity test under the fixed effect model showed no obvious heterogeneity of TRIM5, FAM8A1, and SHFL across different populations. TRIM5 was positively correlated with the remaining 13 genes. By separating patient samples into TRIM5-high and TRIM5-low groups, we found that up-regulated genes in the TRIM5-high group were mainly enriched in virus-related pathways. Immune cell proportion analysis and flow cytometry revealed that naive CD4(+) T cells were significantly decreased while M2 macrophages were increased in the SLE group. TRIM5 expression levels were negatively correlated with naive CD4(+) T cells but positively correlated with M2 macrophages.Conclusion: Our data indicated that TRIM5 might be a key factor that modulates SLE etiology, possibly through naive CD4(+) T cells and M2 macrophages.Keywords: differential gene expression analysis, gene, virus, autoimmune disease

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