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  • Review Article
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MicroRNAs—novel regulators of systemic lupus erythematosus pathogenesis

Abstract

Dysregulation of gene expression can cause complex disease phenotypes. MicroRNAs (miRNAs) are well known to fine-tune cellular gene expression to control immune cell development and regulate adaptive and innate immune responses. Discoveries over the past decade have indicated that aberrant expression of miRNAs is associated with the pathogenesis of multiple immunological diseases, including systemic lupus erythematosus (SLE). Indeed, profiling miRNA expression in blood cells, body fluid and target tissues taken from patients with SLE has revealed unique miRNA signatures when compared with healthy individuals or those with other diseases. Moreover, dysregulation of these miRNAs has also been found to be associated with disease activity and major organ involvement. In our opinion, therefore, miRNAs have the potential to act as biomarkers for the diagnosis and assessment of patients with SLE. This Review provides an overview of the novel cellular and molecular mechanisms that seem to underlie the roles of miRNAs in SLE disease processes, as well as the future therapeutic potential of targeting miRNAs in the management of patients with SLE.

Key Points

  • MicroRNAs (miRNAs) control immune cell differentiation, and regulate innate and adaptive responses; dysregulation of these immunologically important miRNAs can cause systemic autoimmunity and tissue inflammation

  • Patients with systemic lupus erythematosus (SLE) and mouse models of SLE present abnormal miRNA expression patterns, which are associated with disease activity and severity, when compared with healthy controls

  • Differential expression of multiple miRNAs seems to contribute to SLE pathogenesis by regulating the type I interferon pathway, inflammatory cytokine expression, DNA methylation in T cells and local tissue inflammation

  • miRNAs are potential novel biomarkers and could be future therapeutic targets in patients with SLE

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Figure 1: Roles of miRNA in abnormal activation of type I IFN signalling in SLE.
Figure 2: Roles of miRNA in SLE hypomethylation.
Figure 3: Role of miR-125a and miR-21 in regulation of cytokine/chemokine production in T cells in SLE.

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Acknowledgements

This work was partially supported by the National Natural Science Foundation of China (No.30971632, No.81025016) and the Program of the Shanghai Commission of Science and Technology (No.10JC1409300).

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N. Shen and Y. Tang researched data for the article. N. Shen, D. Liang, N. de Vries and P.-P. Tak substantially contributed to the discussion of content, wrote the article and edited the article prior to submission. D. Liang also contributed to the writing of the article.

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Correspondence to Nan Shen.

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Novel roles of miRNAs in immune system (DOC 151 kb)

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Shen, N., Liang, D., Tang, Y. et al. MicroRNAs—novel regulators of systemic lupus erythematosus pathogenesis. Nat Rev Rheumatol 8, 701–709 (2012). https://doi.org/10.1038/nrrheum.2012.142

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