Mesenchymal Stem Cells Control Complement C5 Activation by Factor H in Lupus Nephritis
Haijun Ma,
Chang Liu,
Bingyu Shi,
Zhuoya Zhang,
Ruihai Feng,
Minghao Guo,
Liwei Lu,
Songtao Shi,
Xiang Gao,
Wanjun Chen,
Lingyun Sun
Affiliations
Haijun Ma
Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China; Department of Rheumatology and Immunology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, China
Chang Liu
Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
Bingyu Shi
Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
Zhuoya Zhang
Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
Ruihai Feng
Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
Minghao Guo
Department of Rheumatology and Immunology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, China
Liwei Lu
Department of Pathology and Shenzhen Institute of Research and Innovation, The University of Hong Kong, Hong Kong, China
Songtao Shi
Department of Anatomy and Cell Biology, School of Dental Medicine, University of Pennsylvania, Philadelphia, USA
Xiang Gao
Model Animal Research Center, Nanjing University, Nanjing, China
Wanjun Chen
Mucosal Immunology Section, NIDCR, US National Institutes of Health, Bethesda, MD, USA
Lingyun Sun
Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China; Corresponding author at: Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, Jiangsu 210008, China.
Lupus nephritis (LN) is one of the most severe complications of systemic lupus erythematosus (SLE) caused by uncontrolled activation of the complement system. Mesenchymal stem cells (MSCs) exhibit clinical efficacy for severe LN in our previous studies, but the underlying mechanisms of MSCs regulating complement activation remain largely unknown. Here we show that significantly elevated C5a and C5b-9 were found in patients with LN, which were notably correlated with proteinuria and different renal pathological indexes of LN. MSCs suppressed systemic and intrarenal activation of C5, increased the plasma levels of factor H (FH), and ameliorated renal disease in lupus mice. Importantly, MSCs transplantation up-regulated the decreased FH in patients with LN. Mechanistically, interferon-α enhanced the secretion of FH by MSCs. These data demonstrate that MSCs inhibit the activation of pathogenic C5 via up-regulation of FH, which improves our understanding of the immunomodulatory mechanisms of MSCs in the treatment of lupus nephritis. Keywords: Lupus nephritis, C5, MSCs, FH