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335 Microrna-21 is a critical regulator of autoimmunity through promoting effector and metabolic function of pathogenic th17 cells
  1. X Yu,
  2. D Dai and
  3. N Shen
  1. RenJi Hospital- School of Medicine- Shanghai JiaoTong University, Department of Rheumatology, Shanghai, China


Background and aims Systemic lupus erythematosus is a prototypical autoimmune disease that causes mortality and morbidity worldwide. Recent studies suggest proinflammatory TH17 cells are key pathogenic factors that contribute to lupus nephritis. Our group previously demonstrate that microRNA-21 was highly upregulated in CD4+ T cells from both lupus patients and lupus-prone mice. However, the role of microRNA-21 in pathogenic TH17 cells and they-mediated autoimmune diseases is still unclear. In this study, we systemically dissect the role of microRNA-21 in the differentiation and effector function of pathogenic TH17 cells.

Methods MicroRNA-21 knockout and conditional knockout mice were generated. EAE was induced to study the role of microRNA-21 in pathogenic TH17 cell-mediated autoimmune diseases. RNA-seq, RIP-seq and DAVID bioinformatic analysis were conducted to find key microRNA-21 regulated pathway and molecular targets in pathogenic TH17 cells. Metabolic assays were done to study the glycolytic activity of microRNA-21-deficent pathogenic TH17 cells.

Results In this study, we demonstrate that IL-6-STAT3 signalling induced microRNA-21 is essential for the late stage commitment and maintenance of pathogenic TH17 cells by targeting key regulators. MicroRNA-21-deficient TH17 cells express less pathogenic TH17 signature genes and show less glycolytic activity. Conditional deletion of microRNA-21 in CD4+ T cells protects mice from EAE while loss of microRNA-21 expression by dendritic cells and myeloid cells do not.

Conclusions These findings suggest that microRNA-21 is a novel cell-intrinsic regulator of the commitment and metabolic function of pathogenic TH17 cells. It may be a potential therapeutic candidate with which to reprogram the immune system and help prevent and treat autoimmune diseases.

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