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  2. Reduced mitochondrial-encoded NADH dehydrogenase 6 gene expression drives inflammatory CD4+T cells in patients with systemic lupus erythematosus

Reduced mitochondrial-encoded NADH dehydrogenase 6 gene expression drives inflammatory CD4+T cells in patients with systemic lupus erythematosus

  • Free Radic Biol Med. 2024 Mar:213:79-89. doi: 10.1016/j.freeradbiomed.2024.01.026.
Miheraiy Abdukiyum 1 Xiaojun Tang 2 Nan Zhao 1 Yiyuan Cui 1 Jingjing Zhang 2 Tohtihan Alim 2 Yuanyuan Zheng 1 Wenjing Li 2 Mengxi Huang 1 Xuxue Feng 1 Honghong Yu 1 Xuebing Feng 3
Affiliations

Affiliations

  • 1 Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, China.
  • 2 Department of Rheumatology and Immunology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
  • 3 Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, China; Department of Rheumatology and Immunology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China. Electronic address: fengxuebing@hotmail.com.
Abstract

Abnormal mitochondrial function has been implicated in the progression of systemic lupus erythematosus (SLE), the prototypical autoimmune disease, yet the underlying cause remains unclear. In this study, mitochondrial-encoded NADH dehydrogenase 6 gene (MT-ND6) was identified as having increased m6A methylation and decreased expression in peripheral blood mononuclear cells of SLE patients by MeRIP-seq analysis. MT-ND6 expression was negatively correlated with SLE disease activity index score and 24-h urine protein level, and lower in patients with positive anti-Sm or anti-dsDNA Antibodies. With the reduction of MT-ND6 levels, CD4+ T cells in SLE patients exhibited mitochondrial dysfunction, as evidenced by increased levels of Reactive Oxygen Species (ROS) and mitochondrial ROS and insufficient ATP production. Accordingly, in vitro MT-ND6 silencing induced abnormalities in the above mitochondrial Indicators in CD4+ T cells, and promoted the development of both transcription and inflammatory factors in these cells. In contrast, treatment with targeted mitochondrial antioxidants largely counteracted the silencing effect of MT-MD6. Thus, reduced MT-ND6 in SLE patients may lead to mitochondrial dysfunction through ROS overproduction, thereby promoting inflammatory CD4+ T cells.

Keywords

CD4(+) T cells; Mitochondrial function; NADH-dehydrogenase 6; Systemic lupus erythematosus.

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