Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 492, Issue 3, Pages 453-460Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2017.08.075
Keywords
miR-873; Systemic lupus erythematosus; Th17; Foxol
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Funding
- National Natural Science Foundation of China [81571469]
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lupus erythematosus (SLE) is a chronic autoimmune disease, and its pathogenesis remains mostly unknown. MicroRNAs (miRs) has drawn much attention as a crucial regulator of autoimmune diseases. In this study, we demonstrated that miR-873 expression was significantly up-regulated in patients with SLE, and its expression was positively associated with the disease severity. CD4(+) T cells, especially the Th17 subset, were found to be the major source of miR-873 expression. Using gain-and loss-of-function approaches, we further showed that miR-873 could facilitate the differentiation of CD4(+) T cells into Th17 lineage. Moreover, forkhead box 01 (Foxo1), one member of the Foxo family, was identified as a novel target gene of miR-873, and Foxol has been known as an inhibitor of Th17 cell differentiation. Foxol was observed to be markedly decreased in PBMC of patients with SLE. Notably, in vivo lentivirus-mediated inhibition of miR-873 significantly alleviated the disease severity of spontaneous SLE in MRL/Ipr mice, with down-regulated levels of autoantibodies, proteinuria, and IL-17A. Our data reveal a novel mechanism in which the elevated miR-873 in PBMC of SLE promotes Th17 cell differentiation through down-regulation of Foxol. In vivo blockade of miR-873 may serve as a novel therapeutic approach in the treatment of SLE. (C) 2017 Published by Elsevier Inc.
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