MiR-125a targets effector programs to stabilize Treg-mediated immune homeostasis

Wen Pan, Shu Zhu, Dai Dai, Zheng Liu, Dan Li, Bin Li, Nicola Gagliani, Yunjiang Zheng, Yuanjia Tang, Matthew T. Weirauch, Xiaoting Chen, Wei Zhu, Yue Wang, Bo Chen, Youcun Qian, Yingxuan Chen, Jingyuan Fang, Ronald Herbst, Laura Richman, Bahija Jallal, John B. Harley, Richard A. Flavell, Yihong Yao () and Nan Shen ()
Additional contact information
Wen Pan: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine
Shu Zhu: Yale University School of Medicine
Dai Dai: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine
Zheng Liu: MedImmune LLC
Dan Li: Institute Pasteur of Shanghai, Chinese Academy of Sciences
Bin Li: Institute Pasteur of Shanghai, Chinese Academy of Sciences
Nicola Gagliani: Yale University School of Medicine
Yunjiang Zheng: Yale University School of Medicine
Yuanjia Tang: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine
Matthew T. Weirauch: Cincinnati Children's Hospital Medical Center
Xiaoting Chen: School of Electronic and Computing Systems, University of Cincinnati
Wei Zhu: MedImmune LLC
Yue Wang: MedImmune LLC
Bo Chen: MedImmune LLC
Youcun Qian: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine
Yingxuan Chen: Renji Hospital, Shanghai Institute of Digestive Disease, Shanghai Jiaotong University School of Medicine
Jingyuan Fang: Renji Hospital, Shanghai Institute of Digestive Disease, Shanghai Jiaotong University School of Medicine
Ronald Herbst: MedImmune LLC
Laura Richman: MedImmune LLC
Bahija Jallal: MedImmune LLC
John B. Harley: Cincinnati Children's Hospital Medical Center
Richard A. Flavell: Yale University School of Medicine
Yihong Yao: MedImmune LLC
Nan Shen: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine

Nature Communications, 2015, vol. 6, issue 1, 1-12

Abstract: Abstract Although different autoimmune diseases show discrete clinical features, there are common molecular pathways intimately involved. Here we show that miR-125a is downregulated in peripheral CD4+ T cells of human autoimmune diseases including systemic lupus erythematosus and Crohn’s disease, and relevant autoimmune mouse models. miR-125a stabilizes both the commitment and immunoregulatory capacity of Treg cells. In miR-125a-deficient mice, the balance appears to shift from immune suppression to inflammation, and results in more severe pathogenesis of colitis and experimental autoimmune encephalomyelitis (EAE). The genome-wide target analysis reveals that miR-125a suppresses several effector T-cell factors including Stat3, Ifng and Il13. Using a chemically synthesized miR-125a analogue, we show potential to re-programme the immune homeostasis in EAE models. These findings point to miR-125a as a critical factor that controls autoimmune diseases by stabilizing Treg-mediated immune homeostasis.

Date: 2015
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DOI: 10.1038/ncomms8096

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