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MicroRNA-21 Regulates Metabolic Adaptation of Pathogenic TH17 cells and Controls Autoimmune Inflammation

Xiang Yu, Li Wang, Chao Yao, Rong Qiu, Yangge Cui, Dai Dai, Jun Deng, Guojun Hou, Yan Wang, Jie Qian, Yangye Ou, Yuting Qin, Haibo Zhou, Youcun Qian, Yuanjia Tang, Nan Shen
doi: https://doi.org/10.1101/218545
Xiang Yu
1Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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Li Wang
1Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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Chao Yao
2Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine and Shanghai Institutes for Biological Sciences (SIBS), University of Chinese Academy of Sciences, Chinese Academy of Sciences (CAS), Shanghai, China.
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Rong Qiu
2Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine and Shanghai Institutes for Biological Sciences (SIBS), University of Chinese Academy of Sciences, Chinese Academy of Sciences (CAS), Shanghai, China.
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Yangge Cui
2Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine and Shanghai Institutes for Biological Sciences (SIBS), University of Chinese Academy of Sciences, Chinese Academy of Sciences (CAS), Shanghai, China.
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Dai Dai
3China-Australia Centre for Personalized Immunology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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Jun Deng
3China-Australia Centre for Personalized Immunology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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Guojun Hou
2Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine and Shanghai Institutes for Biological Sciences (SIBS), University of Chinese Academy of Sciences, Chinese Academy of Sciences (CAS), Shanghai, China.
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Yan Wang
2Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine and Shanghai Institutes for Biological Sciences (SIBS), University of Chinese Academy of Sciences, Chinese Academy of Sciences (CAS), Shanghai, China.
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Jie Qian
1Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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Yangye Ou
1Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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Yuting Qin
3China-Australia Centre for Personalized Immunology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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Haibo Zhou
3China-Australia Centre for Personalized Immunology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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Youcun Qian
2Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine and Shanghai Institutes for Biological Sciences (SIBS), University of Chinese Academy of Sciences, Chinese Academy of Sciences (CAS), Shanghai, China.
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Yuanjia Tang
1Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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Nan Shen
1Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
2Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine and Shanghai Institutes for Biological Sciences (SIBS), University of Chinese Academy of Sciences, Chinese Academy of Sciences (CAS), Shanghai, China.
3China-Australia Centre for Personalized Immunology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
4Center for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA.
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Abstract

TH17 cells exhibit great heterogeneity and variable functional states in vivo. However, the precise molecular mechanism for this heterogeneity is poorly understood. Here we demonstrate that homeostatic and pathogenic TH17 cells in vivo show discrete chromatin states at conserved regulatory region of TH17 cell-related transcription factors, metabolic regulators and microRNAs. We find the regulatory region of miR-21 shows great more chromatin accessibility in CNS infiltrating pathogenic TH17 cells compared to ileum homeostatic TH17 cells. We further demonstrate that homeostatic and pathogenic TH17 cells have distinct metabolic states, and miR-21 is essential for the highly glycolytic state of pathogenic TH17 cells. MiR-21-deficient TH17 cells show less glycolytic activity and express less pathogenic TH17 cell signature genes. These findings suggest that miR-21 is a critical regulator for the metabolic adaptation of pathogenic TH17 cells under autoimmune inflammation.

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Posted November 13, 2017.
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MicroRNA-21 Regulates Metabolic Adaptation of Pathogenic TH17 cells and Controls Autoimmune Inflammation
Xiang Yu, Li Wang, Chao Yao, Rong Qiu, Yangge Cui, Dai Dai, Jun Deng, Guojun Hou, Yan Wang, Jie Qian, Yangye Ou, Yuting Qin, Haibo Zhou, Youcun Qian, Yuanjia Tang, Nan Shen
bioRxiv 218545; doi: https://doi.org/10.1101/218545
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MicroRNA-21 Regulates Metabolic Adaptation of Pathogenic TH17 cells and Controls Autoimmune Inflammation
Xiang Yu, Li Wang, Chao Yao, Rong Qiu, Yangge Cui, Dai Dai, Jun Deng, Guojun Hou, Yan Wang, Jie Qian, Yangye Ou, Yuting Qin, Haibo Zhou, Youcun Qian, Yuanjia Tang, Nan Shen
bioRxiv 218545; doi: https://doi.org/10.1101/218545

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