PT  - JOURNAL ARTICLE
AU  - Yu, X
AU  - Dai, D
AU  - Shen, N
TI  - 335 Microrna-21 is a critical regulator of autoimmunity through promoting effector and metabolic function of pathogenic th17 cells
AID  - 10.1136/lupus-2017-000215.335
DP  - 2017 Mar 01
TA  - Lupus Science & Medicine
PG  - A148--A148
VI  - 4
IP  - Suppl 1
4099  - http://lupus.bmj.com/content/4/Suppl_1/A148.3.short
4100  - http://lupus.bmj.com/content/4/Suppl_1/A148.3.full
SO  - Lupus Sci & Med2017 Mar 01; 4
AB  - 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.