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Water-soluble artemisinin derivatives as promising therapeutic immunosuppressants of autoimmune diseases

Cellular & Molecular Immunology volume 14, pages 887–889 (2017)Cite this article

SLE is a refractory chronic autoimmune disease that is characterized by the loss of tolerance to and sustained autoantibody production against self-antigen, which results in the development of immune complex-mediated renal and skin injuries.6 The etiology of SLE is multifactorial and includes genetic susceptibility, epigenetic regulation and environment factors. Administration of SM934 to MRL/lpr mice greatly ameliorates proteinuria and renal lesion and results in decreased levels of serum biochemical indices, inflammatory cytokines and autoantibodies.7 SM934 inhibits both Th1 and Th17 cell responses ex vivo. Furthermore, SM934 significantly restores the B cell compartment in the spleens of MRL/lpr mice; this compound increases the number of quiescent B cells and maintains germinal center B cells, while decreasing the number of activated B cells and plasma cells.8 Consistent with the results obtained in MRL/lpr mice, SM934 inhibits Toll-like receptor ligand-associated B cell activation and plasma cell differentiation in human peripheral blood mononuclear cells. In addition, SM934 treatment for 3 or 6 months dramatically slows the progression of glomerulonephritis and increases the survival rate of lupus-prone female NZB/W F1 mice via inhibiting pathogenic helper T cell development. Increasing evidence has revealed the essential role of the initiation of innate inflammatory responses in the development of lupus, in which macrophages are generally regarded as a bridge between innate and adaptive immunity.9 SM934 promotes IL-10 secretion by macrophages obtained from NZB/W F1 mice and ovalbumin-immunized C57BL/6 mice, as well as by IFN-γ-primed peritoneal macrophages.10

The kidney is often a target of pathogenic renal autoantigen or systemic autoimmune responses.11 Membranous nephropathy, a common manifestation of nephrotic syndromes in adults, is an immune-mediated disease that is distinguished by the deposition of immune complexes in the glomerular basement membrane and podocytes.12 SM934 treatment attenuates kidney injury and renal fibrosis by reducing proteinuria and circulating antibodies, as well as decreasing immune complex deposition in the kidney in a rat model of membrane nephropathy induced by anti-Fx1A serum.13 Furthermore, SM934 can modulate the TGF-β1/Smad signaling pathway and can block tubular epithelial mesenchymal transition.13 This study provides evidence that SM934 may be a treatment option for proteinuric renal diseases.

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Authors and Affiliations

  1. Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuzhongzhi Road, Shanghai, 201203, China

    Heng Li, Jianping Zuo & Wei Tang

  2. College of Pharmacy, University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing, 100049, China

    Heng Li, Jianping Zuo & Wei Tang

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Correspondence to Jianping Zuo or Wei Tang.

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Li, H., Zuo, J. & Tang, W. Water-soluble artemisinin derivatives as promising therapeutic immunosuppressants of autoimmune diseases. Cell Mol Immunol 14, 887–889 (2017). https://doi.org/10.1038/cmi.2017.87

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