Article Text

PDF

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

Abstract

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.

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.